Kurzgesagt – In a Nutshell
Sources – Tattoo Inside
We thank the following experts for their critical reading of the script:
Dr. Maxim Darvin
Charité - Universitätsmedizin Berlin
– Your skin has to solve a huge problem – it is your largest organ and has the most direct contact with the world around you. Trillions of microbes, dirt, insects and vermin can’t be allowed to get inside you – but your skin is also constantly damaged by you moving through the world.
It may not seem much like an organ to you but the skin is actually a complex organ with different cell types. It protects you from bacteria as well as from UV light, chemicals, and mechanical injury. It also regulates body temperature and stores water and fat.
#Yousef H, Alhajj M, Sharma S. Anatomy, Skin (Integument), Epidermis. Retrieved October, 2023
https://www.ncbi.nlm.nih.gov/books/NBK470464/
Quote: “Skin is the largest organ in the body and covers the body's entire external surface. It is made up of three layers, the epidermis, dermis, and the hypodermis, all three of which vary significantly in their anatomy and function. The skin's structure is made up of an intricate network which serves as the body’s initial barrier against pathogens, UV light, and chemicals, and mechanical injury. It also regulates temperature and the amount of water released into the environment.”
– Your body solved this by making your skin a conveyor belt of death. All the skin you see is actually dead stuff. The alive part of your skin cells begins around one millimeter deep, in the skin industrial complex. Stem cells constantly clone themselves producing new skin cells that begin a journey from the inside to the outside.
Skin is broadly divided into three layers: epidermis, dermis and hypodermis (also called subcutaneous fat layer), from top to bottom. The epidermis is further divided into multiple layers: stratum basale, stratum spinosum, stratum granulosum, and stratum corneum, from deep to superficial. The thickness of the epidermis varies across the body, being thickest in palms and soles of the feet and thinnest in eyelids. In the thickest parts, there is a fifth layer called stratum lucidum.
The very top and the very dead layer of skin is called Stratum corneum. And the layer where the proliferating stem cells are is called Stratum Basale (here referred to as “skin industrial complex”).
It takes around a month for the stem cells to move up from Stratum Basale to Stratum corneum. This process is called keratinization. In the stratum corneum they are dead and regularly shed, being replaced by cells from the deeper skin layers.
#Cleveland Clinic. Epidermis. Retrieved December 2023.
https://my.clevelandclinic.org/health/body/21901-epidermis
The main cell types found in the epidermis are:
– Keratinocytes are the primary cell type of the epidermis accounting for approximately 95% of total epidermal cells.
– Basal cells, which are the cells in stratum basale.
– Melanocytes, which are found at the base of the epidermis and make melanin, which gives the skin its color.
– Langerhans’ cells, a special type of dendritic cells
– Merkel’s cell, sensor cells
– Stratum basale is a single layer of basal cells, separated from the dermis by the basement membrane (aka basal lamina which is made up of collagen fibers). The cells found in this layer are active stem cells that are constantly producing keratinocytes. Keratinocytes are the primary cells in epidermis and produce and store the protein keratin. All keratinocytes are produced from this single layer of cells, which are constantly going through mitosis to produce new cells. This layer also contains melanocytes and merkel cells. There are also finger-like projections into the dermis which make the connection with the epidermis stronger.
– Stratum spinosum (8-10 cell layers) has irregular, polyhedral cells with cytoplasmic processes reaching outward and contacting neighboring cells. A type of dendritic cell called the Langerhans cells are interspersed among the keratinocytes in this layer and function as a macrophage by engulfing bacteria, foreign particles, and damaged cells that occur in this layer. Keratinocytes here start the keratin production and release a water-repelling glycolipid that helps prevent water loss from the body. As new keratinocytes arrive from stratum basale, the keratinocytes of the stratum spinosum are pushed up to the stratum granulosum.
– Stratum granulosum (3-5 cell layers) diamond shaped cells. They become flatter here and their cell membranes get thicker. They produce keratin, which is fibrous, and keratohyalin, which accumulates as lamellar granules within the cells. The lamellar granules contain the glycolipids that get secreted to the surface of the cells and function as a glue, keeping the cells stuck together.
– Stratum lucidum (2-3 cell layers) present in thick skin, like in the palms and soles.
– Stratum corneum (20-30 cell layers), is the uppermost layer, made up of keratin and horny scales made up of dead keratinocytes. Cells here dont have This dry, dead layer helps prevent microbes and dehydration, and provides a mechanical protection against abrasion for the more delicate layers below. The dead keratinocytes here secrete defensins which are part of our first immune defense.
In each layer keratinocytes are slightly different and they change as they move up.
#Keratinocyte. Labster. 2022.
https://theory.labster.com/keratinocyte/
Quote: “Keratinocytes are created from basal cells in the stratum basale, where they receive plenty of nutrients to start assembling fibers of keratin. Upon reaching the stratum spinosum layer, keratinocytes start connecting with each other through desmosomes and produce more bundles of keratin while still getting nutrients to stay alive. In the stratum granulosum, the cells are still tightly connected through desmosomes with visible lamellar bodies, keratohyalin, and keratin molecules embedded in the cytoplasm. Lamellar bodies are responsible for releasing a lipid-rich secretion that serves as a water repellent sealant for this and upper layers of the epidermis. Keratohyalin assembles keratin intermediate filaments into keratin. The organs of the keratinocytes pushed into the stratum lucidum are deteriorated, and the cells are no longer alive. Keratyhoalin is secreted out of the cells and transformed into a transparent protein called eleidin. Eleidin tightens the connection between the cells, facilitating the protective and water-repellent function of the skin. In the most upper layer of epidermis stratum corneum, dead keratinocytes become corneocytes. These cells are filled with keratin and eventually shed off the skin. They are no longer connected to each other.”
#Malgosia Wilk-Blaszczak (Alford, Campo-Velez, Dorch). Human Anatomy Lab Manual. Retrieved December 2023.
https://eknizky.sk/wp-content/uploads/2020/02/Human-Anatomy-Lab-Manual-1535056949.pdf
Keratinocytes are linked to each other and hold in place through different mechanisms, collectively creating the epidermal barrier.
#Lefèvre-Utile A, Braun C, Haftek M, Aubin F. Five Functional Aspects of the Epidermal Barrier. 2021
#Yousef H, Alhajj M, Sharma S. Anatomy, Skin (Integument), Epidermis. Retrieved October, 2023
https://www.ncbi.nlm.nih.gov/books/NBK470464/
Quote: “The epidermis is the outermost layer of the skin, and protects the body from the environment. The thickness of the epidermis varies in different types of skin; it is only .05 mm thick on the eyelids, and is 1.5 mm thick on the palms and the soles of the feet. The epidermis contains the melanocytes (the cells in which melanoma develops), the Langerhans' cells (involved in the immune system in the skin), Merkel cells and sensory nerves. The epidermis layer itself is made up of five sublayers that work together to continually rebuild the surface of the skin”
#Sandby-Møller, Poulsen and Wulf. Epidermal Thickness at Different Body Sites: Relationship to Age, Gender, Pigmentation, Blood Content, Skin Type and Smoking Habits. 2003.
https://www.medicaljournals.se/acta/download/10.1080/00015550310015419/
– Each new generation pushes the older ones further up. As your skin cells mature, they interlock with each other and produce Lamellar bodies, tiny bags that squirt out fat to create a waterproof coat that closes any gaps between them. And then, they dry out and kill themselves, merging together into inseparable clumps. This wall of dead corpses is consistently pushed upwards. Up to 50 layers of dead cells cover your whole body and are constantly replaced by new cells moving up.
#Layers of epidermis. Labster Theory Pages. 2022
https://theory.labster.com/epidermis_layers/
Quote: “Stratum granulosum consists of 3 to 5 layers of keratinocytes that slowly start to undergo apoptosis (programmed death). Their organelles start to degenerate as they move further away from the source of nutrition (blood vessels embedded in the dermis). In this layer, keratinocytes are rich in keratohyalin and lamellar granules. Keratohyalin molecules assemble keratin, and lamellar granules release a lipid-rich secretion that fills spaces between cells of the stratum granulosum, lucidum, and corneum. The secretion is water repellant, aiding water entry and loss regulation through the skin.”
#The life cycle of a horny cell. 2003.
https://www.personal-care.basf.com/news-media/photos-and-illustrations/photosandillustrations-detail/2003/10/01/the-life-cycle-of-a-horny-cell
#Omolu A, Bailly M, Day RM. Assessment of solid microneedle rollers to enhance transmembrane delivery of doxycycline and inhibition of MMP activity. 2017
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241162/
Quote: “The primary barrier to intradermal drug delivery (IDD) and transdermal drug delivery (TDD) is the stratum corneum (SC) which forms the outermost layer of the epidermis (Vandervoort & Ludwig, 2008). It is a thin hydrophobic layer of cells, formed mainly of corneocytes, and has a thickness that varies from body site to body site – as thin as nine cell layers on the eyelid and as thick as 50 cell layers on the soles of the feet (Ya-Xian et al., 1999). This barrier makes therapeutic access with IDD to susceptible tissue during the early stages of chronic wounds challenging.”
#Menon et al. An overview of epidermal lamellar bodies: Novel roles in biological adaptations and secondary barriers. 2018.
https://www.jdsjournal.com/article/S0923-1811(18)30130-0/fulltext
Quote: “The epidermal lamellar bodies (LBs) are specialized organelles that contain pro-barrier lipids imparting a fully lamellar internal structure, but also other cargoes such as enzymes (lipid metabolizing and proteolytic), enzyme inhibitors, and antimicrobial peptides. Thus, the LB secretory system, by virtue of delivering these cargoes to the stratum corneum (SC) interstices, is essential for forming the various skin barriers located in the SC.”
#Mahanty and Setty. Epidermal Lamellar Body Biogenesis: Insight Into the Roles of Golgi and Lysosomes. 2021.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387949/pdf/fcell-09-701950.pdf
Quote: “These cells are further subjected to late-stage differentiation and gradually lose their intracellular organelles while generating a new set of organelles called lamellar bodies (eLBs), which form the granulosum layer. These eLBs undergo exocytosis and generate the lipid sheets/barrier. Lastly, the cells of the granular layer undergo terminal differentiation, which forms SC (reviewed in Bikle et al., 2012). These cells are also called corneocytes (lack intracellular organelles) that remain embedded in lipid sheets produced by eLBs of the granular layer. The sequential changes in intracellular organelle dynamics, including the nucleus, are shown in the sublayers of skin (Akinduro et al., 2016). Extracellular ascending calcium gradient (Ca2+) and a descending nutrient gradient exist from the base of the epidermis. Note that the deformation of the nucleus initiates at the spinosum layer and eliminated through nucleophagy in the upper layers of the epidermis.”
– Every hour, you shed around 200,000,000 dead skin cells and all the dirt or bacteria that are stuck to them.
#ScienceDaily. New insights into skin cells could explain why our skin doesn't leak. 2016
https://www.sciencedaily.com/releases/2016/11/161129114910.htm
Quote: “Humans lose 200,000,000 skin cells every hour. During a 24-hour period, a person loses almost five thousand million skin cells. It has been a challenge for scientists to explain how this colossal shedding process can occur without there being a break in the skin barrier.”
There are different numbers circulating for the daily amount of shed skin cells. The number we use originated from a 1995 book Handbook of non-invasive methods and the skin.
#Leonard M. Milstone. Epidermal desquamation. 2004.
https://www.jdsjournal.com/article/S0923-1811(04)00098-2/fulltext
Quote: “Collection chambers were devised to collect scale reproducibly from small areas of skin, and a variety of methods confirmed their reliability for quantifying scale (reviewed in [4]). The relevance of those methods was validated by the observation that the number of squames removed by a short, controlled rinse of the epidermal surface with mild detergent correlated closely with the number of squames shed spontaneously over a longer period of time [5]. Extrapolation of data from such sampling methods is the origin of estimates that humans shed between 2 x10^8 and 10 x10^8 cells per day [5].”
There is a whole microbiota you are carrying all over your skin, as well as viruses, fungi and mites occasionally.
#Byrd et al. The human skin microbiome. 2018.
https://www.nature.com/articles/nrmicro.2017.157
Quote: “The immune system has evolved closely with resident microorganisms in the skin to allow the maintenance of commensal partners and the elimination of possible pathogens. To operate optimally, the skin microbiota, epithelial cells and innate and adaptive arms of the immune system need to communicate effectively. Keratinocytes can begin this dialogue by sensing microorganisms, especially pathogen-associated molecular patterns (PAMPs), through pattern recognition receptors (PRRs)22. Binding of PAMPs to PRRs triggers innate immune responses, resulting in the secretion of antimicrobial peptides that can rapidly kill and inactivate a diverse range of microorganisms, including fungi, bacteria and parasites. As a first line of defence against pathogens, some antimicrobial peptides are constitutively expressed114, whereas the expression of others can be transient and controlled by members of the skin microbiota121,122”
– Below the conveyor belt of death lies the dermis. It's full of structural tissue and cells, tiny blood vessels, sensory cells that report to nerve endings, the roots of your hairs, sweat glands regulating your temperature.
The dermis is the middle layer of the skin. It is a tough but flexible structure due to the collagen that it is made up of. It contains pain and touch receptors, as well as blood and lymph vessels, hair follicles, sweat glands, collagen bundles, fibroblasts, nerves, sebaceous glands.
The main cell types of the dermis are fibroblasts who are responsible for producing collagen. Collagen makes a structural mesh in the dermis providing elasticity and support to the skin.
#OpenStax College. Provided by: Rice University. Module 6: The Integumentary System. Retrieved December 2023.
https://courses.lumenlearning.com/suny-ap1/chapter/layers-of-the-skin/
It is thicker than the epidermis, averaging 1-4 mm, and has two broadly defined zones, the papillary dermis and the reticular dermis.
#Cleveland Clinic. Dermis. Retrieved December 2023.
https://my.clevelandclinic.org/health/body/22357-dermis
Quote: “Reticular dermis: The reticular layer is the bottom layer of your dermis. It’s thick, and it contains blood vessels, glands, hair follicles, lymphatics, nerves and fat cells. A net-like structure of elastin fibers and collagen fibers surrounds the reticular dermis. These fibers support your skin’s overall structure, as well as allow it to move and stretch.
Papillary dermis: The papillary layer is the top layer of your dermis. It’s much thinner than the reticular dermis. It consists of collagen fibers, fibroblast cells, fat cells, blood vessels (capillary loops), nerve fibers, touch receptors (Meissner corpuscles) and cells that fight bacteria (phagocytes). The papillary dermis extends to the basement layer of the epidermis layer. They form a strong bond that connects like interlocking fingers.”
– And of course loads of immune cells, guarding your flesh right below the moving border wall.
#Nguyen and Soulika. The Dynamics of the Skin’s Immune System. 2019.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515324/pdf/ijms-20-01811.pdf
Quote: “Skin-resident myeloid cells include Langerhans cells, dermal dendritic cells, macrophages, mast cells, and eosinophils. Neutrophils are rarely found in healthy skin and thus are not “skin-resident cells.” However, neutrophils populate the skin in inflammatory conditions and after a wound, and they will be discussed in the wound healing sections of this review. Skin-resident myeloid cells contribute to skin homeostasis by secreting growth factors needed for the survival of keratinocytes, fibroblasts, and endothelial cells. In addition, they maintain optimal tissue function by phagocytosing debris and apoptotic cells, supporting vasculature integrity, and promoting tolerance. In inflammatory conditions, myeloid cells respond immediately and produce pro-inflammatory mediators that drive the activation of cells in the local vicinity and infiltration of the affected site by peripheral immune cells. Skin myeloid cells also serve as a liaison between the innate and adaptive immune system.”
#Tavakoli and Klar. Advanced Hydrogels as Wound Dressings. 2020.
https://www.researchgate.net/publication/343589010_Advanced_Hydrogels_as_Wound_Dressings/figures?lo=1
Quote: "[Figure Caption] Figure 1. The structure of human skin consisting of three primary layers-the epidermis, the dermis, and the hypodermis. The two inserts (right site) show their detailed cellular structure at higher magnification. The epidermis consists mainly of keratinocytes, melanocytes, and Langerhans cells. The dermis contains fibroblasts, neutrophils, mast cells, and dermal dendritic cells embedded within the dermal matrix rich in collagen and elastin. Beneath the dermis lies the subcutaneous adipose tissue (hypodermis) containing mesenchymal stem cells."
#Pasparakis, Haase & Nestle. Mechanisms regulating skin immunity and inflammation. 2014.
https://www.nature.com/articles/nri3646/figures/1
– The world explodes. Half a dozen monoliths the size of skyscrapers slam through the fifty layers of dead cells, deep into the dermis, ripping huge holes into the skin – only to retreat and smash through the tissue again about twice a second. Tens of thousands of cells are violently killed right away, ripped into pieces or damaged beyond repair.
Tattooing is basically 200-350 micron diameter needles repeatedly puncturing the skin at a depth of around 2 mm, leaving the ink particles in the papillary dermis. On average, about 1 mg of ink is injected per cm² of tattoo. There is a range of frequencies that the tattoo machines operate with and how many times it punctures would also depend on the number of individual needles at the tip, but we went with an average frequency within commonly mentioned values.
A skyscraper is a minimum of 150 m, the average human height 1.65 m and a needle would go in 2 mm. So for a skin cell of 20 micrometers in diameter, 2000/20 ~ 100 times its size which is on par with 150 m /1.65 ~ 90 times.
#Gareau D. Automated identification of epidermal keratinocytes in reflectance confocal microscopy. 2011
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077366/
Quote: “Making the reasonable assumption that the nucleus diameter is slightly less than half that of the entire cell the mean nuclear diameter (a = 8.6 μm) reported here compares well to the published diameter8 for the entire cell: 15 to 35 μm. The maturation cycle, where spherical spinous keratinocytes near the basal layer develop into wider and flatter granular keratinocytes indicates healthy skin.”
#What Speed Should my Tattoo Machine be? Retrieved October 023
https://tattoomack.com/blogs/tattoo-information-and-news/what-speed-should-my-tattoo-machine-be
Quote: “First, it's important to understand that the speed of your tattoo machine is measured in hertz (Hz). One hertz is equal to one cycle per second. Most tattoo machines operate at a frequency between 50 and 150 Hz, with some machines capable of operating at even higher frequencies.”
#Grant et al. Tattoo ink nanoparticles in skin tissue and fibroblasts. 2015.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464189/pdf/Beilstein_J_Nanotechnol-06-1183.pdf
Quote: “The tattooing process involves inserting ink pigment of the desired colour into the dermis layer of the skin. This is carried out by first dipping a needled tattoo instrument into the coloured ink before applying to the skin. The oscillating ink coated needle punctures the skin in the range of 100 times per second, depositing the ink pigments 1.5 to 2 mm below the skin surface.
It depends on the type of the tattoo machine and the application, there can be a single one or more than 20 needles soldered together. Large numbers of needles are typically used for shading and filling work, whereas smaller numbers are used for lines. More tightly packed sets are used for drawing definitive lines while more loosely packed sets for shading.
#Frank Rosenkilde. 21 - 30: Tattoo Machines, Needles and Utilities. 2015.
https://karger.com/books/book/174/chapter/5110083/Tattoo-Machines-Needles-and-Utilities
Quote: “The thickness, length and point of a needle are all essential for the type of tattoo that is wanted. What we call a needle actually consists of several needles that are soldered together in various ways. A ‘round' needle that is tightly soldered into a pointed shape may hold up to fifteen needles. This is used for outlining a tattoo. A soldering of up to fifteen needles will be used for colouring and shading. Magnums/flatshaders are soldered in layers. The larger the tattoo (for instance, a back tattoo with background), the larger the number of needles.”
#Pazos et al. Tattoo Inks for Optical Biosensing in Interstitial Fluid. 2021.
Quote: “Tattoo pigments are injected into the dermis between 0.4 and 2.2 mm in depth; the ideal penetration depth is 2.0 mm as shallower injection rapidly fades while deeper penetration damages the subcutaneous tissue.[9]”
Quote: "[Figure Caption] Figure 1. Tattoo machines, needles, and inks. A) Types of tattoo machines and tattoo needles 1. Tomas Edison's patent No.196747 for his electric pen from 1877. Reproduced with permission. [23] Copyright 1877, United States Patent Office 2. Dual-coil tattoo machine 3. Rotative machine 4. Pneumatic machine A-Tip, B-Needle, C-Tube, D-Grip, E-Energy system: Coil/rotative motor/air piston, F-Armature bar, G-Contact screw 5. Needle types RL-Round liner, RS-Round shader, F-Flat, and M-Magnum M1 weaved, M2 double-stacked, MR curved. B) Composition of tattoo inks."
In the article linked below you can find a slow motion footage of needles movement:
#Adrian Cho. That tattoo needle doesn’t do what you think it’s doing. 2022
https://www.science.org/content/article/tattoo-needle-doesn-t-do-what-you-think-it-s-doing
Quote: “Unlike a hypodermic needle, a tattoo needle does not inject liquid when it is sunk into the skin. Rather, as the solid, ink-coated stylus descends, it opens a small hole up to 2 millimeters deep. Only as the needle pulls out of the skin does the vacuum in the hole draw ink into the skin—as Lawal showed in this video in which a clear gel serves as a surrogate for flesh. He says he could find no reference to the effect in the scientific literature—although it’s clearly familiar to tattoo artists.”
– Luckily, you did your research and chose a responsible tattoo artist who properly disinfected their tools and your skin. But you only ever get 99.9% of all bacteria, and some of the survivors made it into your flesh.
Disinfectant generally kills most of the bacteria before they become a problem so infection occurs only in a small percentage of people.
#Laux et al. A medical-toxicological view of tattooing. 2016
https://pubmed.ncbi.nlm.nih.gov/26211826/
Quote: “From a medical perspective, tattooing involves overcoming the skin barrier and thus carries some risk of infection because the skin surface is not sterile. About 1–5% of tattooed people have tattoo-related bacterial infections after receiving a tattoo. These infections can be superficial local skin infections or more severe systemic cases, with pathogens encompassing specific bacterial strains as well as multibacterial communities, fungi, or blood-borne viruses such as hepatitis C or B or HIV.2,4,17,18 Although diffi cult to treat, infections with fungi and viruses are rare.2,3,19 Bacterial infections are far more prominent and culprits consist of, among others, group A Staphylococci spp (eg, Staphyloccus aureus), Streptococci spp (eg, Streptococcus pyogenes), mycobacteria (nontuberculous and tuberculous) and pseudomonads.4,20–23”
– To put it mildly, your immune system is not amused at all! All the death and destruction wakes up hundreds of thousands of Macrophages in your dermis, that rush into the open wounds to defend you. Immediately they start killing bacteria, release chemicals that call for reinforcements and order your blood vessels to open up and make your dermis swell up with fluid.
#Grant et al. Tattoo ink nanoparticles in skin tissue and fibroblasts. 2015.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464189/pdf/Beilstein_J_Nanotechnol-06-1183.pdf
Quote: “Thus, the needle penetrates the skin through the epidermis and into the papillary layer of the dermis, where the ink particles accumulate. As with any type of trauma to the dermis, the first response of the body is to stop the resultant bleeding to form a clot. Then the skin tissue swells (edema) followed by a migration of immune system cells to the wound site (neutrophils and macrophages) in order to phagocytose foreign substances, cell debris and microbes. Any damaged collagen in the wounded papillary dermis is then repaired through the action of fibroblasts, ultimately laying down scar tissue. Over long periods of time the tattoo ink particles can be found to gradually move to the deeper dermis (i.e., reticular dermis), which gives the tattoo a faded and blurred appearance. Importantly, after tattoo ink insertion associated pigment particles can be found to leave the skin via its vasculature and enter the lymphatic system (nodes) [3].”
#Lawal, Rohilla & Marston. Visualization of drug delivery via tattooing: effect of needle reciprocating frequency and fluid properties. 2022.
https://link.springer.com/article/10.1007/s12650-021-00816-5
Quote: “After the procedure, the body's immune system kicks into overdrive (from the thousands of micro injuries that just occurred) and responds by; inflammation which is immediately triggered by tissue phagocytes at the scene of injury. These cells release histamines that cause a transient increase in vasodilation and vascular permeability accompanied with the release of cytokines that signal the next phase; influx of monocytes through the blood vessels (aided by vasodilation). Monocytes become macrophages when they reach the site of injury, after which they either consume the deposited ink and traverse to the lymph nodes for excretion or remain in the dermis (a reason for the seemingly permanent nature of tattoos) (Petersen and Roth 2016).”
#Islam, P.S., Chang, C., Selmi, C. et al. Medical Complications of Tattoos: A Comprehensive Review. 2016.
https://link.springer.com/article/10.1007/s12016-016-8532-0
Quote: “With a fresh tattoo, the ink extends from the surface of the skin to the dermis. There is disruption of the epidermal basement membrane and some necrosis of the involved dermal and epidermal cells. Studies on fresh tattoos (using pigment-type ink) demonstrate phagocytosis of the pigment in the first 2 h by exudated polymorphonuclear leukocytes. Thereafter, no pigment granules are present in the leukocytes [18]. At about 24 h, pigment aggregates in cytoplasmic phagosomes in keratinocytes, macrophages, mast cells, and fibroblasts [19]. Langerhans cells may identify foreign antigens and transport them to the draining lymph nodes invoking a subsequent lymphocytic response. Due to needling
of the basement membrane, some of the dermal pigment may be extruded back through transepidermal elimination. At 1 month, transepidermal elimination is still occurring and pigment is found in keratinocytes, macrophages, and fibroblasts. Once the basement membrane has been restored, presumably no further transepidermal elimination occurs. Tattoo ink may be found in draining lymph nodes”
– But worse than the hundreds of wounds and a few invaders is the tidal wave of chemicals that floods your tissue. Tattoo ink can be made from hundreds of substances, some may even be toxic or carcinogenic. Most are from heavy metals like lead, nickel, chromium dissolved in distilled water.
Tattoo inks are generally colorants made up of metallic salts that are carried in a solvent along with binders, surfactants and other additives. However, tattoo ink manufacturers aren't required to disclose their ingredients in the US for example so there is no definitive information on the content of each product. But there are some research efforts to analyze inks for the ingredients.
Modern tattoo inks contain organic pigments, but they can also contain heavy metals as chromophores, shading additives, or as contaminants. Titanium, barium, aluminium, and copper are predominantly used as colorants, whereas antimony, arsenic, cadmium, chromium, cobalt, lead, and nickel tend to be contaminants. Some metal oxides (eg, aluminium oxide, titanium oxide) are sometimes added as nanoparticles to create special
effects.
#Laux et al. A medical-toxicological view of tattooing. 2015.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60215-X/fulltext
Quote: “Meanwhile metals such as titanium, copper, and aluminium are found in ink in concentrations as high as 180·9 g/kg, 31·3 g/kg, and 5·9 g/kg, respectively (Boccha B, unpublished), and a survey from Denmark16 reported high concentrations for toxic metals such as chromium (31 mg/kg), nickel (18 mg/kg), and lead (10 mg/kg).”
#Islam, P.S., Chang, C., Selmi, C. et al. Medical Complications of Tattoos: A Comprehensive Review. 2016.
https://link.springer.com/article/10.1007/s12016-016-8532-0
Quote: “Traditional tattoos use particulate matter pigment suspended in a diluent to deliver the material to the dermis. Most traditional colored inks involve the use of metals, including heavy metals. Black tattoo ink is formulated with a combination of iron salts and carbon. More recently, dyes have been used in tattooing, in part to avoid the use of heavy metals and in part to provide a wider variety of color and to generate more vibrant colors. Dyes are soluble compounds that attach to a substrate by electrostatic forces. The dyes used for tattooing are created for printer ink and for paint colorants. These modern-day colorants are mainly organic, containing azo or polycyclic pigments. Nonetheless, antimony, cadmium, lead, chromium, cobalt, nickel, and arsenic may still be present as contaminants [9]. Furthermore, many tattoo artists prefer to use traditional granular pigments and may store and use inks and powders for decades. Spectrophotometric analysis of trace metals has revealed the presence of multiple elements at levels exceeding the traditionally accepted safe limit of 1 μg/g [16, 17 (see Table 2)]”
#Jennifer Ouellette. Scientists explore chemistry of tattoo inks amid growing safety concerns. 2022
Quote: “Typical tattoo ink contains one or more pigments (which give the ink its color) within a "carrier package" to help deliver the pigments into the skin. The pigments are the same as those used in paints and textiles. They can be either small bits of solids or discrete molecules, such as titanium dioxide or iron oxide (for white or rust-brown colors, respectively). As for the carrier packages, most ink manufacturers use grain or rubbing alcohol, sometimes with a bit of witch hazel added to the mix to help the skin heal after the tattooing process. There may also be other additives to adjust the viscosity and keep pigment particles suspended in the carrier package.”
There is also a website where researchers share the ingredients of the inks they studied:
#Swierk Research Group. Department of Chemistry. Binghamton University
#Schreiver et al. Synchrotron-based ν-XRF mapping and μ-FTIR microscopy enable to look into the fate and effects of tattoo pigments in human skin. 2017.
https://www.nature.com/articles/s41598-017-11721-z#Sec8
Quote: “Tattoo pigments consist of either inorganic colorful metals and its oxides, or of polyaromatic compounds, all of which are thought to be biologically inert. It can thus be expected to find a broad range of elements in tattooed human tissue—among them the sensitizers nickel (Ni), chromium (Cr), manganese (Mn), and cobalt (Co)—as parts of color-giving pigments or element contamination 14–17. Besides carbon black, the second most commonly used ingredient of tattoo inks is titanium dioxide (TiO2), a white pigment usually applied to create certain shades when mixed with colorants. The toxicity of TiO2 depends on its speciation (crystal structure) which can be either rutile or the more harmful photocatalytically active anatase18. The latter can lead to the formation of reactive oxygen species when exposed to sunlight. Delayed healing is thus often associated with white tattoos, along with skin elevation and itching19”
#McGovern V. Metal Toxicity: Tattoos: Safe Symbols? Environ Health Perspect. 2005
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280436/
Quote: “Titanium and aluminum are often used as colorants in tattoos; more worrisome, inks using nonmetal colorants may include traces of antimony, arsenic, beryllium, chromium, cobalt, lead, nickel, and selenium (AESI filed over the latter eight metals). Sivas says the ink used for a 3 by 5 inch tattoo contains 1–23 micrograms of lead, versus the 0.5 micrograms per day permitted under Proposition 65.”
#Jennifer Ouellette. Scientists explore chemistry of tattoo inks amid growing safety concerns. 2022
Quote: “They found that many ingredients didn't appear on the manufacturers' labels, such as one ink that contained ethanol even though it was not listed on the label. And 23 of the inks analyzed thus far show evidence of an azo-containing dye. Such pigments are usually inert, but exposure to bacteria or UV light can cause them to degrade into a nitrogen-based compound that potentially could cause cancer.
Furthermore, says Swierk, "Often the particle sizes used in tattoo inks are very small—less than 100 nanometers in diameter. When you get down to that size regime, you start to have concerns about nanoparticles penetrating into cells, getting into the nucleus and doing damage, possibly causing cancer." About half of the 18 inks analyzed with electron microscopy had particles in this worrisome size range.”
#Schreiver et al. Synchrotron-based ν-XRF mapping and μ-FTIR microscopy enable to look into the fate and effects of tattoo pigments in human skin. 2017.
https://www.nature.com/articles/s41598-017-11721-z#Sec8
Quote: “Tattoos contribute to the elemental load of lymph nodes. A central aim of this study was to assess to what extent tattooing increases the proportion of toxic elements in the body. We found Al, Cr, Fe, Ni and Cu quantitatively elevated in skin and lymph node specimens using ICP-MS analysis (Table 1 and Supplementary Table S2). For donor 4, Cd and Hg concentrations were found increased only in the lymph nodes, but not in the analyzed skin sections. These elements probably result from other tattoos that were not part of this study or other routes of exposure drained through the same lymphatic tissue. Non-quantitative evaluation of the survey scans revealed the presence of Ti, presumably derived from TiO2, in all tattooed skin samples but not in controls.”
Apart from the materials in ink, there can also be nickel and chromium deposit from the needle.
#Schreiver, I., Hesse, B., Seim, C. et al. Distribution of nickel and chromium containing particles from tattoo needle wear in humans and its possible impact on allergic reactions. 2019
https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-019-0317-1
Quote: “Here, we report the deposition of nano- and micrometer sized tattoo needle wear particles in human skin that translocate to lymph nodes. Usually tattoo needles contain nickel (6–8%) and chromium (15–20%) both of which prompt a high rate of sensitization in the general population. As verified in pig skin, wear significantly increased upon tattooing with the suspected abrasive titanium dioxide white when compared to carbon black pigment.”
– The battlefield is now a wild mix of dead cell parts, a few panicked bacteria, blood and bodily fluids, platelet cells trying to close wounds, more and more fresh immune cells and the flood of tattoo ink.
Tattooing process causes wounds and would be followed by the normal wound-healing process, of which the steps are summarized below.
#Nguyen and Soulika. The Dynamics of the Skin’s Immune System. 2019.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515324/pdf/ijms-20-01811.pdf
Quote: “The wound healing process consists of four tightly orchestrated and largely overlapping phases: hemostasis, inflammation, proliferation, and remodeling (Figure 1).
In hemostasis, the skin tissue isolates the injured area from the environment and prevents further bleeding by forming a clot. In the case of an insult, tissue factor (TF), normally located in the subendothelial spaces of the skin, is exposed to blood via compromised vasculature. This initiates the coagulation cascade, during which platelets adhere to components of extracellular matrix constituents, secrete their granular contents, and aggregate [364,365].
[...]
The inflammatory phase is characterized by infiltration of the wound by immune cells, such as neutrophils, monocytes, and lymphocytes. The milieu of the wound during this phase consists of high levels of pro-inflammatory mediators, which serve to recruit other immune cells from the periphery. The purpose of the inflammatory phase is for the host to ward off any pathogens that have entered the wound site and prevent infections. In addition, phagocytes clear out necrotic debris.
[...]
The proliferative phase is marked by expansion of skin-resident cells including keratinocytes, fibroblasts, and endothelial cells [368]. During this phase, keratinocytes expand and migrate to restore the barrier function of the epidermis
[...]
In the remodeling phase, the injured tissue attempts to restore its original architecture. Many immune cells, endothelial cells, and myofibroblasts undergo apoptosis or are removed from the wound, leaving mostly the newly developed extracellular matrix and collagen fibers.”
#Xue M, Jackson CJ. Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring. 2015.
https://europepmc.org/article/PMC/4352699
– On the scale of your cells, clumps of ink particles are huge – if you were the size of a cell, they’d range from big dogs to small office buildings.
If we take the skin cell to be an average diameter of 20 micrometers, particles in the ink with sizes on a range of 5 nanometer to larger than a micrometer, in various shapes like needles, platelets, cubes, bars, and a number of irregular shapes. But they agglomerate in dermis forming chunks larger than skin cells.
Following are some electron microscopy images of various tattoo ink particles:
#Bocca et al. Size and metal composition characterization of nano- and microparticles in tattoo inks by a combination of analytical techniques. 2017.
https://pubs.rsc.org/en/content/articlelanding/2017/ja/c6ja00210b
Quote: "Figure Caption: Fig. 1 TEM images of the tattoo inks: (A) ink number 1 (monthly red); (B) ink number 2 (ice blue); (C) ink number 3 (mean green); (D) ink number 4 (bright orange); (E) ink number 5 (deep violet); (F) ink number 6 (black outlining); (G) ink number 7 (grasshopper green); (H) ink number 8 (dark chocolate); (I) ink number 9 (true black)."
#Grant et al. Tattoo ink nanoparticles in skin tissue and fibroblasts. 2015.
https://www.beilstein-journals.org/bjnano/articles/6/120
Quote: “Light microscopy analysis of tattooed skin section revealed some interesting features. Figure 6a shows a transverse section of histologically stained tattooed skin, with the epidermal region uppermost in the image. Clumps of tattoo ink have dispersed throughout the upper and lower dermis. However, close inspection of a deep dermal blood vessel (Figure 6b) showed regions of tattoo ink scattered in the vessel wall as well as inside (peri)-vascular cells. A recent study, using a model system of mice tattooed with a commonly used ink to investigate the transportation and photo-decomposition of tattoo pigment particles [30], reported that the amount of ink in the mouse skin had reduced by 32 ± 16% of its initial value 42 days after tattooing. ”
Following light microscopy image is of a tattooed arm skin. Large deposits of dark ink particles distributed in a clumped manner in the dermis; scale bar 75 μm.
#Grant et al. Tattoo ink nanoparticles in skin tissue and fibroblasts. 2015
https://www.beilstein-journals.org/bjnano/articles/6/120
Quote: “The collagen fibrils here have a strong degree of parallel orientation, which would suggest that this region may well be scar tissue that was formed following the tattoo process. In a recent AFM study we compared scar tissue and healthy skin tissue and demonstrated that greater alignment of collagen fibrils occurs in scar tissue, as well as highlighting the reduction in the biomechanical performance of the scar tissue [25]. However, due to patient confidentiality it was not possible to find out more about how long the subject had the tattoo. Further, as the subject was 62 years old, the skin was also aged, including photo-aged from exposure of the forearm to UV irradiation. From multiple scans over a number of sections of tattooed skin tissue, it is clear that there were many regions of highly agglomerated ink particles, as shown in Figure 3. These agglomerations can be larger than the dermal cells, thereby changing the nature of the interaction between the pigment and the surrounding skin cells.”
Image above shows the agglomerate of ink particles and collagen fibers around it.
#Atlas of Plant and Animal Histology. Cell types / Keratinocyte. Retrieved October 2023.
https://mmegias.webs.uvigo.es/02-english/8-tipos-celulares/queratinocito.php
Quote: “Keratinocyte stem cells are found in the stratum basale. They are rounded to columnar in shape, about 6-10 µm in size, and show more affinity for basic dyes than differentiated keratinocytes because of their high content in ribosomes.
[...]
The stratum spinosum is found just above the stratum basale (Figures 2 and 3). It is made up of more or less polyhedral keratinocytes of about 10 to 15 µm in size, larger than those in the stratum basale, showing more eosinophilic cytoplasm and one or two clearly visible nuclei.”
#Gareau D. Automated identification of epidermal keratinocytes in reflectance confocal microscopy. 2011
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077366/
Quote: “Making the reasonable assumption that the nucleus diameter is slightly less than half that of the entire cell the mean nuclear diameter (a = 8.6 μm) reported here compares well to the published diameter8 for the entire cell: 15 to 35 μm. The maturation cycle, where spherical spinous keratinocytes near the basal layer develop into wider and flatter granular keratinocytes indicates healthy skin.”
#Schreiver et al. Synchrotron-based ν-XRF mapping and μ-FTIR microscopy enable to look into the fate and effects of tattoo pigments in human skin. 2017.
https://www.nature.com/articles/s41598-017-11721-z#Sec8
Quote: “The contribution of tattoo inks to the overall body load on toxic elements, the speciation of TiO2, and the identities and size ranges of pigment particles migrating from sub epidermal skin layers towards lymph nodes have never been analytically investigated in humans before. The average particle size in tattoo inks may vary from <100 nm to >1 µm20. Therefore most tattoo inks contain at least a small fraction of particles in the nano range.”
#Devcic et al. Immediate and Sustained Effects of Cobalt and Zinc-Containing Pigments on Macrophages. 2022.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343594/pdf/fimmu-13-865239.pdf
– Your immune system has one main job: Identify what is not you and smash it until it is dead. The Macrophages are desperately trying to do that. Like tiny octopuses, they extend arm-like structures and begin pulling the ink particles inside. Usually, when a Macrophage has eaten an enemy, it showers it in acid to dissolve it. But this doesn’t work with the ink. They try and try but nothing works, the particles do not react in any way.
#Devcic et al. Immediate and Sustained Effects of Cobalt and Zinc-Containing Pigments on Macrophages. 2022.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343594/pdf/fimmu-13-865239.pdf
Quote: “After intradermal injection, pigments (under micro- or nanoparticulate form) are internalized by three main cells: fibroblasts, neutrophils, and macrophages. Neutrophils are mainly present at the site of injection immediately after the injection due to mechanical injuries comprising blood losses, superficial infections (3), inflammations, etc. caused by the insertion of the needle into the dermis. These short-lived cells (about 24h) are then quickly eliminated by macrophages via the efferocytosis process and are consequently absent from the tattoo site in the long term. Fibroblasts internalize a low quantity of pigments contrary to macrophages which are professional phagocytic cells and ensure the lifelong persistence of tattoo inks in the dermis due to successive cycles of pigment capture, release and recapture. Indeed, dead macrophages are replaced by mostly new monocyte-derived macrophages, or, to a lesser extent, via a local process of self-renewal (20, 21).”
Quote: “3.3.2 The Pigments Are Slowly Degraded in Macrophages Macrophages engulf particles via the phagolysosomal pathway. Consequently, pigments internalized by macrophages were certainly exposed to an environment that is both acidic and oxidizing, which could cause metal ions to be released from the pigments into the cells. To evaluate this phenomenon, we measured the soluble ion content of cellular extracts after exposure to the pigments, either at the end of the 24h exposure phase or at the end of the 72h post-exposure period. The results, displayed in Table 2, show distinct differences between the end of the exposure period on the one hand, and the end of the recovery period on the other.”
#Sil, Wong and Martinez. More Than Skin Deep: Autophagy Is Vital for Skin Barrier Function. 2018.
https://www.frontiersin.org/articles/10.3389/fimmu.2018.01376/full
Quote: “Macrophages are skin resident phagocytes surveilling the epidermis and dermis (2). They help in maintaining the immunotolerant environment of the skin (2, 92). Specialized macrophages in the skin called melanophages can engulf melanocyte fragments and melanin. These melanocyte fragments and melanin are processed by autophagy (70–72). In leprosy patients, skin-derived macrophages have significant upregulation of autophagy genes, including Beclin1 and Atg14 (73).”
– And this is just the particles small enough to be devoured. By now the larger chunks are surrounded by thousands of your structural skin cells and macrophages that are nomming on them, bathing them in acid and attack chemicals trying to destroy and kill them. But they are not moving even a tiny bit.
Macrophages can usually gulp down particles of a few micrometers (smaller than 0.5 microns to approximately 2 microns). So bigger clumps of ink can not be ingested either by them or by fibroblasts (structural skin cells). Fibroblasts are not professional phagocytic cells like macrophages but they are normally involved in clearing up dead cells for example in wound healing.
#Pacheco, White and Sulchek. Effects of Microparticle Size and Fc Density on Macrophage Phagocytosis. 2013.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0060989
Quote: ”We show the internalization efficiency of small polystyrene particles (0.5 µm to 2 µm) is significantly affected by changes in Fc ligand density, while particles greater than 2 µm show little correlation between internalization and Fc density. We found that while macrophages can efficiently phagocytose a large number of smaller particles, the total volume of phagocytosed particles is maximized through the non-specific uptake of larger microparticles. Therefore, larger microparticles may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles can deliver bio-active substances to a greater percentage of the macrophage population.”
#Baranov et al. Modulation of Immune Responses by Particle Size and Shape. 2021
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927956/
Quote: “The size of the particles is also an important determinant for immune activation. Hydroxyapatite crystals smaller than 1–2 µm caused more TNF-α release by cultured human primary macrophages compared to 6 and 14 µm sized particles (175), likely because of more efficient activation of the inflammasome as discussed above (166).”
– They vacuum up all the particles they can fit into their bodies and surround the larger ones trapping them in the only prison they can build: themselves. Bit by bit, the ink inside thousands of tiny wounds moves inside millions of immune cells that freeze in place forever.
#Zaba LC, Fuentes-Duculan J, Steinman RM, Krueger JG, Lowes MA. Normal human dermis contains distinct populations of CD11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages. 2007
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1957542/
Quote: “Skin tattoos provided a second functional study: the phagocytic activity of tissue macrophages. Pigment granules were found in lysosomal-like cellular structures, and cells containing pigment stained uniformly with CD163. The fate of tattoo pigment injected into dermal tissues has been studied in the past, and fibroblasts were considered to be the primary long-term reservoir of the pigment granules, with pigment in occasional macrophages (30, 31). However, our data suggest that macrophages are indeed a significant store of the dermal pigment. The cells with pigment were CD163+ and BDCA-1–, were round, had numerous microvillous projections, and the pigment was contained within membrane-bound structures (lysosomes). These characteristics are consistent with macrophages (31, 32).”
Quote (Figure Caption): “(A) Tattoo skin section (0.5 μm) stained with toludine blue. Cells containing green tattoo dye in their cytoplasm (black arrow) surrounded a blood vessel. (B) Electron microscopy of a tattoo showed that dye particles (red arrow) were membrane bound (blue arrow) within the cytoplasm of a cell with multiple microvillus protrusions (green arrow). (C and D) Cells containing green tattoo dye particles stained for CD163 (D) but not BDCA-1 (C). Scale bar: 10 μm (A, C, and D); 200 nm (B).”
Following image shows the outline of macrophages (green), nucleus of macrophages (blue) and ink particles in red.
#Devcic et al. Immediate and Sustained Effects of Cobalt and Zinc-Containing Pigments on Macrophages. 2022.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343594/pdf/fimmu-13-865239.pdf
– On the outside you don’t notice any of this. Your new tattoo is fresh and the colors vibrant. Your skin hurts and is irritated and swollen. But wounds heal, tiny holes close, dead cells are replaced. Bit by bit, the conveyor belt of death does its job, shedding dead cells ripe in color, replacing them with fresh and clean ones. Your tattoo becomes a little less vibrant, now the ink is no longer on your skin but inside it.
#Bäumler. Absorption, Distribution, Metabolism and Excretion of Tattoo Colorants and Ingredients in Mouse and Man: The Known and the Unknown. 2015.
https://karger.com/books/book/174/chapter/5111478/Absorption-Distribution-Metabolism-and-Excretion
Quote: “After tattooing skin, pigment particles are exclusively found in the cytoplasm of cells in membrane-bound structures identified as secondary lysosomes [35]. Also, macrophages may contain pigment particles. At first view, the injected tattoo colorants seem to stay in skin forever. However, three major mechanisms may reduce the concentration of colorants that is initially placed in the skin. First, part of the colorant may leave the skin with the bleeding during or directly after tattooing. Second, part of the colorant may be transported away from the skin via the lymphatic or blood vessel system. Third, part of the colorant is decomposed months or years after tattooing because the pigments in the dermis are repeatedly exposed to different light sources, in particular, solar radiation, including UV radiation. Azo pigments are chemically unstable when exposed to UV radiation [14, 15].”
Ink pigments can travel to lymph nodes via passive transport and active transport via macrophages. This is especially true several weeks after the injection of tattoo ink when around 30% of the ink has been eliminated via blood or lymphatic circulation.
– Over time your Macrophages get old and die and new ones come in to gobble up the ink and keep it in place. But sometimes a tiny bit of ink escapes. Most of it is recaptured and locked in place, but not always the exact same place.
Experiments on mice suggest that tattoos stay because ink particles are taken up by one macrophage after the other. When a macrophage dies, it releases the particles inside. Then another macrophage comes along, clears away the cellular cadaver and eats up the ink particles. Since the ink particles are too big to get drained into the lymph nodes, they get stuck in there until another macrophage ingests them.
#Baranska et al. Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal. 2018
https://rupress.org/jem/article-pdf/215/4/1115/1759956/jem_20171608.pdf
Quote: “Although the dermis lacked macrophages for approximately 1 wk after DT treatment and it took several more weeks for the incoming macrophages to scavenge the released cell-free tattoo pigments, no macroscopic modification of the tattoo occurred.
Before our study, the longevity of the undefined tattoo-pigment-laden cells found in the dermis was thought to be in the same order of that of a human adult, thereby accounting for long-term tattoo persistence (Fig. 10 B). Based on the present results, an alternative model for long-term tattoo persistence can be proposed. It takes into consideration the facts that the macrophages found in the dermis of adult mice are continuously replenished from circulating monocytes to compensate for the loss of dying macrophages and that most of the tattoo particles that are released from macrophages after DT treatment of CD64dtr mice remain in situ and are recaptured by incoming macrophages. According to the pigment capture–release–recapture model (Fig. 10 A), in physiological conditions, when tattoo-pigment-laden macrophages die during the course of adult life, neighboring macrophages recapture the released pigments and ensure in a dynamic manner the macroscopic stability and long-term persistence of tattoos. Note that, in contrast to dermal cDCs, dermal macrophages do not have the capacity to migrate to draining LNs under normal and inflammatory conditions (Tamoutounour et al., 2013), an essential property for insuring tattoo persistence. Whether the pigment capture–release–recapture model of tattoo persistence applies to humans remains to be determined. In the case of the melanophages found in the human dermis, it has been suggested that they persist for years through longevity rather than continual renewal (Bigley et al., 2011).”
#Pazos et al. Tattoo Inks for Optical Biosensing in Interstitial Fluid. 2021.
https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.202101238
Quote: “The persistence of tattoos can be explained by macrophages” physiological ability to ingest and store melanin pigment. The ink particles do not have a homogeneous size; macrophages ingest the small particles and eliminate them through the lymphatic system while larger particles remain suspended in the extracellular dermis matrix or are collected by macrophages that cannot break them down due to their size and remain stored in macrophages” cytoplasmic vacuoles.[44] When the macrophage dies, the pigment is released and recaptured by the new generation of macrophages (Figure 4A). Tattoo pigments can go through consecutive cycles of capture–release– recapture without any tattoo elimination.[45] It is possible to identify the location of the pigments using flow cytometry, as untattooed skin scatters less light.[44] Other theories suggest that tattoo persistence depends on macrophage longevity more than macrophage renewal[42] since the skin’s melanophages have the slowest turnover timescales.”
Quote (Figure Caption): “Figure 4. Tattoo persistence. A) Cycle of capture–release–recapture of the tattoo ink by the macrophages in the skin. 1) Photo of a macrophage with ink inside. 2) Photo of a new macrophage entering the cycle. Reproduced with permission.[44,45] Copyright 2018, Rockefeller University Press. Scale bar, 10 μm. B) 1) Macrophage with the tattoo pigment inside ready for diphtheria toxin (DT) treatment. 2) Pigment free in the extracellular matrix after 2 days of DT treatment. 3) Recapture of the pigment by a new macrophage after 90 days of DT treatment. Reproduced with permission. [44] Copyright 2018, Rockefeller University Press. Macrophages from the tail of CD64dtr mice. Bar = 10 μm.”
#Nguyen and Soulika. The Dynamics of the Skin’s Immune System. 2019.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515324/pdf/ijms-20-01811.pdf
Quote: “Macrophages are found in the dermal layer of the skin and require IL-34 for survival [86,150]. Two sources of dermal macrophages have been identified so far. The first source is embryo-derived progenitors that seed the skin prenatally and are self-renewing in a similar fashion to LCs [126]. The second and major source of dermal macrophages is circulating monocytes (monocyte-derived macrophages) that mature once they reach the skin. This population replenishes roughly every 10 days [151,152]. Monocytes that give rise to dermal macrophages express lymphocyte antigen 6C (Ly6C), and home to the skin in a CCR2-dependent manner [129]. As monocytes mature into skin-resident macrophages, the expression of CCR2 is downregulated [153]. CD64 expression is prominent on dermal macrophages and is used as a marker to differentiate them from the dDCs [152,153]. CD36, DC-SIGN, and IL-10 are highly expressed by macrophages isolated from healthy skin, suggesting that they adapt an immunoregulatory phenotype [153,154]. In steady state, macrophages remove cellular debris [129,153], and have also been implicated in homeostatic hair regeneration [54,155]. Macrophages can be localized at post-capillary venules in the skin and secrete chemokines that drive the recruitment of neutrophils [156]. However, the depletion of macrophages does not translate into a reduction of neutrophils in the skin in wounds [152,157], indicating that dermal macrophages are dispensable for neutrophil infiltration.”
– You notice that as your tattoo fades out a bit and turns less sharp and crisp at its edges. Some of the ink escapes the tattoo entirely. It rides fluids flowing from your tissue and spreads around your body, another reason why tattoo ink should ideally not be poison.
#Sepehri et al. Tattoo Pigments Are Observed in the Kupffer Cells of the Liver Indicating Blood-Borne Distribution of Tattoo Ink. 2017.
Quote: “Results: TEM identified intracellular tattoo pigments in the skin and in lymph nodes. TEM in both groups of tattooed mice showed tattoo pigment deposits in the Kupffer cells in the liver, which is a new observation. TEM detected no pigment in other internal organs. Light microscopy showed dense pigment in the skin and in lymph nodes but not in internal organs. Conclusion: The study demonstrated black and red tattoo pigment deposits in the liver; thus, tattoo pigment distributed from the tattooed skin via the bloodstream to this important organ of detoxification. The finding adds a new dimension to tattoo pigment distribution in the body, i.e., as observed via the blood in addition to the lymphatic pathway.”
There is also evidence that smaller nanoscale particles can get to lymph nodes.
#Schreiver et al. Synchrotron-based ν-XRF mapping and μ-FTIR microscopy enable to look into the fate and effects of tattoo pigments in human skin. 2017.
https://www.nature.com/articles/s41598-017-11721-z#Sec8
Quote: “In this investigation, we found a broad range of tattoo pigment particles with up to several micrometers in size in human skin but only smaller (nano)particles transported to the lymph nodes. The exact size limit preventing this translocation is unknown yet. The deposit of particles leads to chronic enlargement of the respective lymph node and lifelong exposure. With the detection of the same organic pigments and inorganic TiO2 in skin and lymph nodes, we provide strong analytical evidence for the migration of pigments from the skin towards regional lymph nodes in humans. So far, this only has been assumed to occur based on limited data from mice and visual observations in humans13, 35. We also were able to prove the presence of several toxic elements, such as Cr and Ni, derived from tattooing. However, elemental deposits in lymph nodes which were not found in the corresponding skin revealed that tattooing might not have been the only route of exposure in these particular individuals whose tissues were removed after their demise”
– Your immune system also kind of doesn’t want you to remove tattoos – usually the ink is shot at with lasers, which heats up the particles until they break into smaller chunks, cooking your brave Macrophages in the process. With every round of lasering, more of your tattoo is broken down and carried away by fluids. But also every time new Macrophages rush into the tattoo to lock the ink in place.
#Pazos et al. Tattoo Inks for Optical Biosensing in Interstitial Fluid. 2021.
https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.202101238
Quote: “Lasers heat the particle and before the particle distributes the heat around its surface, the laser repeats the pulse, and the particle deforms and breaks into smaller particles. Lasers also lyse the macrophages.[44,46] The pulse duration must be briefly than the thermal calm time of the ink particles, for example, nanoseconds. The smaller pigment particles are removed by dermal macrophage cells and lymphocytes through the lymph nodes in the weeks following each laser procedure, therefore, it is important to space laser sessions at least six weeks apart.[47] When tattoos inks are a mixture of different colors, it causes a broad absorption spectrum making them more challenging for removal.[46,47] Dark pigments are easier to remove as black absorbs all wavelengths of light.”
#Laux et al. A medical-toxicological view of tattooing. 2015.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60215-X/fulltext
Quote: “Laser removal is less extreme and routinely preferred in absence of allergic reactions. The corresponding wavelength-induced thermophotolysis allows selective targeting of colourants without destroying the skin. The preferred three types of lasers are Q-switched versions of the ruby laser (λ=694 nm; effective against black, blue, and green), the Nd:YAG laser (λ=1064 nm and 532 nm; effective against black and dark blue or red orange and some yellows), and the alexandrite laser (λ=755 nm; effective against black, blue, and green).68,72 From four to more than ten treatment sessions are needed to rid an individual of their unwanted tattoo. In some cases, complete removal is never achieved (eg, particularly for multicoloured tattoos), which is frequently caused by inorganic pigments such as iron, zinc, and titanium oxides. Furthermore the degradation products of lasercleaved dyes can lead to unforeseen immune reactions.”