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Severe thickening of the pulmonary arteries induced by an acquired immune response

This figure shows photographs taken through a microscope of a normal lung (B, E), and of lungs from mice immunized and challenged with a fungal antigen (Aspergilllus antigen; C, D, F, G).  The stars indicate pulmonary arteries, please note the thickened arterial wall in the immunized and challenged animals (C, D)  that consists of cuffs of smooth muscle cells (F, G) and contains proliferating cells (G).  Panels H-J show the quantification of the  data.  Reprinted with permission of the Journal of Experimental Medicine.






IL-13 & the control of the state of activation of dendritic cells in the lungs

These figures show data obtained with a flow cytometer, an instrument that measures the fluorescence of cells.  The brightness of fluorescence of the cells is determined by the intensity of labeling with specific antibodies.  In Panel A, the flow cytometry data of control mice (shaded areas) are digitally overlayed with the data of mice challenged with Interleukin 13 (IL-13, dark lines).  The data  show that cells washed from the lungs of mice challenged with Interleukin-13 (IL-13) contain activated dendritic cells, expressing higher levels of CD11c, CD11b, MHCII, CD40, CD86 (dark lines are shifted to the right of the gray-shaded areas).  In Panel B, cells stained with control antibody are shown with dark lines and digitally overlayed (gray shaded areas) with the fluorescence of cells stained with an antibody specific to MHCII.  The intensity of staining of cells washed out of the lungs of control mice (PBS), immunized mice challenged with fungal antigen (Asp. Ag & control prot.), and immunized mice challenged with antigen and given an inhibitor of IL-13 (Asp. Ag & IL-13Ra2-Fc) is indicated by the % positive cells, and by the measurement of the mean fluorescence intensity (MFI).  Panel B shows that treatment with the IL-13 inhibitor decreases the percent positive cells, and the intensity of staining (MFI) with the anti-MHCII antibody indicating a decrease in the state of activation of lung dendritic cells.   Reprinted with permission of the Journal of Immunology.



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Selection of significant publications (chronological order): 

  • Daley, E., Emson, C., Guignabert, C., de Waal Malefyt, R., Louten, J., Kurup, V.P., Hogaboam, C., Taraseviciene-Stewart, L., Voelkel, N.F., Rabinovitch, M., Grunig, E., Grunig, G. 2008. Pulmonary Arterial Remodeling Induced by a Th2 Immune Response,  J. Exp. Med., published January 28, 2008, 10.1084/jem.20071008. link to full text
  • Ainsworth, D. M., B. Wagner, M. Franchini, G. Grunig, H. N. Erb, and J. Y. Tan. Time-dependent alterations in gene expression of interleukin-8 in the bronchial epithelium of horses with recurrent airway obstruction.  Am. J. Vet. Res. 2006. 67: 669-677. link to full text
  • Padilla, J., Daley, E., Chow, A., Robinson, K., Parthasarathi, K., McKenzie, A.N.J., Tschernig, T., Kurup, V.P., Donaldson, D.D., Grünig, G. IL-13 regulates the immune response to inhaled antigens.  J. Immunol. 2005. 174(12): 8097-8105. link to full text
  • Grünig, G., A. Banz and R. de Waal-Malefyt.  Molecular Regulation of Th2 Immunity by Dendritic Cells. Pharmacology & Therapeutics 2005. 106: 75-96. ; doi:10.1016/j.pharmthera.2004.11.004
  • Ainsworth, D. M., G. Grünig, M. B. Matychak, J. Young, B. Wagner, H. N. Erb, and D. F. Antczak. Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells. Vet. Immunol. Immunopathol 2003. Nov 15;96 (1-2): 83-91. link to full text
  • Grünig, G., Kurup, V.P. Animal Models of Allergic Bronchopulmonary Aspergillosis. Frontiers in Biosci. 2003. 8 (January 1), e157-171. link to full text
  • Ford, G. J., Rennick, D., Venkayya, R., McArthur, C., Donaldson, D.D., Kurup, V.A., Warnock, M., Grünig, G. IL-13 and IFNγ - interactions in lung inflammation. J. Immunol. 2001. 167: 1769-1777.  link to full text
  • Clemons, K.V., G. Grunig, R.A. Sobel, L.F. Mirels, D. Rennick, and D.A.Stevens. Role of IL-10 in invasive aspergillosis: increased resistance of IL-10 gene knockout mice to lethal systemic aspergillosis. Clin. Exp. Immunol. 2000. 122:186-192. link to full text
  • Grimaldi, J.C., Yu, N.X., Grünig, G., Seymour, B.W.P., Cottrez, F., Robinson, D.S., Hosken, N., Ferlin, W.G., Wu, X., Soto, H., O’Garra, A., Howard, M.C., Coffman, R.L. Depletion of eosinophils in mice through the use of antibodies specific for C-C chemokine receptor 3.  J. Leukocyte Biol. 1999. 65: 846-853. link to full text
  • Kleiber, C., Grünig, G., Jungi, T., Schmucker, N., Gerber, H., Davis, W.C. and Straub, R. Phenotypic analysis of bronchoalveolar lavage fluid lymphocytes in horses with chronic pulmonary disease. J. Vet. Med. A 1999. 46: 177-184.
  • Grünig, G., Warnock, M.L., Wakil, A.E., Venkayya, R., Brombacher, F., Rennick, D.M., Sheppard D., Mohrs, M., Donaldson, D.D., Locksley, R.M. and Corry, D.B. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1998. 282: 2261-2263. link to full text
  • Corry, D.B., Grünig, G., Habeida, H., Kurup, V.P., Warnock, M.L., Sheppard D,, Rennick, D.M. and Locksley, R.M. Requirements for allergen-induced airway hyperreactivity in T and B cell-deficient mice. Mol. Med. 1998. May;4(5):344-355.
  • Grünig, G., Corry, D.B., Leach, M.W., Seymour, B.W.P., Kurup, V.P. and Rennick, D. Interleukin-10 is a natural suppressor of cytokine production and inflammation in a murine model of allergic bronchopulmonary aspergillosis. J. Exp. Med. 1997. 185: 1089-1100.  link to full text
  • Ellis Neyer, L., Grünig, G., Fort, M., Remington, J.S., Rennick, D. and Hunter, C.A. Role of Interleukin-10 in regulation of T-cell-dependent and T-cell-independent mechanisms of resistance to Toxoplasma gondii. Inf. Immun. 1997. 65: 1675-1682. link to full text
  • Berg, D.J., Kühn, R., Rajewsky, K., Müller, W., Menon, S., Davidson, N., Grünig, G. and Rennick, D. Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance. J. Clin. Invest. 1995. 96: 2339-2347. link to full text 
  • Grünig, G., Triplett, L., Canady, L. K., Allen, W.R. and Antczak, D.F. The maternal leukocyte response to the endometrial cups in horses is correlated with the developmental stages of the invasive trophoblast cells. Placenta 1995. 16: 539-559. ; doi:10.1016/S0143-4004(05)80005-0. 
  • Grünig, G. and Antczak, D.F. Horse trophoblasts produce tumor necrosis factor alpha but not interleukin 2, 4, or interferon gamma. Biol. Reprod. 1995. 52: 531-539. link to full text
  • Grünig, G., Himmler, A. and Antczak, D.F. Cloning and sequencing of horse interferon gamma cDNA. Immunogenetics 1994. 39: 448-449.
  • G. Grünig, Hulliger, C., Winder, N.C., Hermann, M., Jungi, T.W., and Von Fellenberg, R. Spontaneous and lipopolysaccharide-induced expression of procoagulant activity by equine lung macrophages in comparison with blood monocytes and blood neutrophils. Vet. Immunol. Immunopathol. 1991. 29: 295-311. ; doi:10.1016/0165-2427(91)90021-4.
  • Grünig, G., Hermann, M., Winder, N.C., and Von Fellenberg, R. Procoagulant activity in respiratory tract secretions from horses with chronic pulmonary disease.  Am. J. Vet. Res. 1988. 49: 705-709.
  • Grünig, G., Hermann, M., Howald, B., Winder, N.C. and Von Fellenberg, R. Partial divergence between airway inflammation and clinical signs in equine chronic pulmonary disease.  Equine Vet.J. 1989. 21: 145-148. link to full text
  • Grünig, G., Von Fellenberg, R., Maier, R., and Corboz, L. Elastase-producing microorganisms in horse lungs: Their possible role in the pathogenesis of chronic pulmonary disease in the horse.  Equine Vet. J. 1986. 18: 396-400. link to full text