Induction of vascular addressins and adhesion molecules in the pancreas of IFN-gamma transgenic mice.
"Vascular addressins" play an important role in lymphocyte homing to chronic inflammatory areas. However, it is not yet known which cytokines induce vascular addressins and other adhesion molecules in vivo. Because IFN-gamma induces adhesion molecules in vitro, we tested the ability of IFN-gamma to induce vascular addressins and other adhesion molecules in vivo employing a transgenic mice model that expresses IFN-gamma in pancreatic beta-cells and develops insulitis (Ins-IFN-gamma mice). Two vascular addressins were induced in the transgenic pancreata. The first was MadCAM-1, a mucosal vascular addressin recognized by MECA-367 and required for lymphocyte homing to Peyer's patches. The second was a peripheral lymph node vascular addressin recognized by MECA-79 and required for homing to peripheral nodes. ICAM-1 was expressed on ductal epithelial cells, endothelial cells, and the majority of infiltrating lymphocytes as well as its ligand LFA-1. Lymphocyte-deficient transgenic mice were also induced to express vascular addressins and ICAM-1, suggesting that probably IFN-gamma itself stimulated the expression of those molecules, not cytokines secreted from infiltrating lymphocytes. LPAM and L-selectin, potential counter-receptors for vascular addressins, were expressed on infiltrating lymphocytes. These results underscore the importance of IFN-gamma as an inducer of vascular addressins in vivo.
Lee
M S
MS
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Sarvetnick
N
N
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000096:biosynthesis*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D004727:Endothelium / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins; D016023:Integrins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000235:genetics*; D019041:L-Selectin; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D009088:Mucoproteins; D010179:Pancreas / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; C069886:L-selectin counter-receptors; D016169:Lymphocyte Function-Associated Antigen-1; C504265:MADCAM1 protein, human; D008565:Membrane Proteins; D009088:Mucoproteins; C071777:integrin alpha4beta7; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D007371:Interferon-gamma