Human Leukocyte Subpopulations from Inflamed Gut Bind to Joint Vasculature Using Distinct Sets of Adhesion Molecules

• Published in: The Journal of immunology (1950) Vol. 166; no. 7; pp. 4650 - 4657
• Main Authors: Salmi, Marko, Jalkanen, Sirpa
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.04.2001
• Subjects: adhesion molecules; Amine Oxidase (Copper-Containing) - genetics; Amine Oxidase (Copper-Containing) - pharmacology; Amine Oxidase (Copper-Containing) - physiology; Antibodies, Blocking - pharmacology; Antibodies, Monoclonal - pharmacology; Cell Adhesion - immunology; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Cell Adhesion Molecules - pharmacology; Cell Adhesion Molecules - physiology; Cell Line, Transformed; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Genetic Vectors - immunology; Genetic Vectors - pharmacology; Humans; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - pathology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Leukocytes - immunology; Leukocytes - metabolism; Leukocytes - pathology; Ligands; Lymphocyte Activation; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphocytes - pathology; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - metabolism; P-Selectin - metabolism; Recombinant Proteins - pharmacology; Synovial Membrane - blood supply; Synovial Membrane - immunology; Synovial Membrane - pathology; Transfection
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.7.4650

Reactive arthritis can be triggered by inflammatory bowel diseases. We hypothesized that migration of mucosal immune cells from inflamed gut to joints could contribute to the development of reactive arthritis. Here we isolated gut-derived leukocytes from patients with Crohn's disease and ulcerative colitis. Using function-blocking mAbs and in vitro frozen section adhesion assays we studied whether these cells bind to synovial vessels and which molecules mediate the interaction. The results showed that mucosal leukocytes from inflammatory bowel diseased gut bind well to venules in synovial membrane. Small intestinal lymphocytes adhered to synovial vessels using multiple homing receptors and their corresponding endothelial ligands (CD18-ICAM-1, alpha(4)beta(7)/alpha(4)beta(1)-integrin-VCAM-1, L-selectin-peripheral lymph node addressins, and CD44). Of these, only ICAM-1 significantly supported binding of immunoblasts. In contrast, P-selectin glycoprotein ligand-1-P-selectin interaction accounted for practically all synovial adherence of mucosal macrophages. In addition, blocking of vascular adhesion protein-1 significantly inhibited binding of all these leukocyte subsets to joint vessels. We conclude that different leukocyte populations derived from inflamed gut bind avidly to synovial vessels using distinct repertoire of adhesion molecules, suggesting that their recirculation may contribute to the development of reactive arthritis in inflammatory bowel diseases.