Investigating infectious and inflammatory disease using zebrafish
The Immune system protects us against infection by a variety of means, including inflammation.
Inflammation is a process by which the body’s white blood cells and chemical products protect us from infection and foreign substances such as bacteria and viruses.
Different leucocytes have different roles
Neutrophils and macrophages are white blood cells (leucocytes). They can scavenge debris and they often arrive first at a site of injury, such as a cut. They release chemicals and toxins that can attract other white blood cells and destroy germs and dead tissue.
They also stimulate the movement of plasma from the blood into the wounded area, causing it to swell. This combination leads to inflammation of the area around the wound, which is why when a cut is healing, the area around it goes red and often feels hot and itchy. In fact the pus that can come out of a cut (or a spot) is mostly made up of dead neutrophils that have cleaned something up and then died having done their job.
The green cells in the following movie are white blood cells, in this case neutrophils, moving around in a live transgenic zebrafish. They are looking for debris and germs to clean up. The cells have been labelled with Green Fluorescent Protein (GFP):
Normally the inflammation lasts only for a short amount of time whilst the damage is repaired (we call this acute inflammation). However, sometimes things go wrong and the inflammation carries on, leading to chronic inflammation. This can cause a lot of damage to the surrounding tissue, and is mostly caused by the chemicals and toxins released by the white blood cells.
This damage causes the symptoms of many diseases, including rheumatoid arthritis, atherosclerosis and hay fever.
Inflammation in zebrafish
We can cause inflammation (an inflammatory response) in anaesthetised fish larvae by making a small injury at the end of the tail. By watching the GFP labelled leucocytes migrating around the fish and then to the wounded area we can learn how white blood cells behave during an inflammatory response.
We can also see how the inflammation is terminated, which needs to occur to avoid the progression to dangerous chronic inflammation. By looking at different zebrafish mutants we are beginning to understand some of the genes required to induce a good immune response to injury and also what processes are involved in stopping it.
We can also use this approach to look at how drugs can affect the behaviour of the leucocytes. The drugs may increase how many go to the wound, how fast they get there or how quickly they leave. Identifying drugs in this way will hopefully lead to the discovery of new treatments for inflammatory diseases.
The video below shows green labelled neutrophils in a whole zebrafish embryo filmed for an hour: