Human leukocyte subpopulations from inflamed gut bind to joint vasculatureusing distinct sets of adhesion molecules

Reactive arthritis can be triggered by inflammatory bowel diseases. We hypo thesized that migration of mucosal immune cells from inflamed gut to joints could contribute to the development of reactive arthritis. Here we isolate d 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 mo lecules mediate the interaction. The results showed that mucosal leukocytes from inflammatory bowel diseased gut bind well to venules in synovial memb rane. Small intestinal lymphocytes adhered to synovial vessels using multip le homing receptors and their corresponding endothelial ligands (CD18-ICAM- 1, alpha (4)beta (7)/alpha (4)beta (1)-integrin-VCAM-1, L-selectin-peripher al lymph node addressins, and CD44). Of these, only ICAM-1 significantly su pported binding of immunoblasts. In contrast, P-selectin glycoprotein ligan d-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 infl amed gut bind avidly to synovial vessels using distinct repertoire of adhes ion molecules, suggesting that their recirculation may contribute to the de velopment of reactive arthritis in inflammatory bowel diseases.