INCREASED EXPRESSION OF CELL-ADHESION MOLECULE P-SELECTIN IN ACTIVE INFLAMMATORY BOWEL-DISEASE

The pathogenic changes of inflammatory bowel disease (IBD) depend on m igration of circulating leucocytes into intestinal tissues. Although l eucocyte rolling and tenuous adhesion are probably regulated by induci ble selectins on vascular endothelia, Little is known about the expres sion of these molecules in Crohn's disease and ulcerative colitis. Usi ng immunohistochemistry on surgically resected specimens, this study i nvestigated endothelial P-selectin (CD62, granular membrane protein-14 0) in frozen sections of histologically uninvolved tissues adjacent to inflammation (Crohn's disease=10; ulcerative colitis=10), from highly inflamed areas (Crohn's disease=20; ulcerative colitis=13), and from normal bowel (n = 20). By Light microscopy, two forms of P-selectin im munoreactivity were detected that apparently corresponded ultrastructu rally to stored and released distributions. Compared with the normal g ut, there was a 3.7-fold increase of P-selectin immunoreactivity on ve ins (p < 0.0001), venules (p < 0.0001), and capillaries (p < 0.05) in the highly inflamed gut, without differences between Crohn's disease a nd ulcerative colitis. In the uninvolved gut, P-selectin expression wa s similar to that seen in normal controls, except for a focal increase of P-selectin in the vicinity of small lymphocyte aggregates. The dra matic upregulation of P-selectin in the inflamed tissue and its potent ial role in leucocyte trafficking support the concept of P-selectin bl ocking therapy for the control of active IBD.