Increased expression of cell adhesion molecule P-selectin in active inflammatory bowel disease.
The pathogenic changes of inflammatory bowel disease (IBD) depend on migration of circulating leucocytes into intestinal tissues. Although leucocyte rolling and tenuous adhesion are probably regulated by inducible selectins on vascular endothelia, little is known about the expression of these molecules in Crohn's disease and ulcerative colitis. Using immunohistochemistry on surgically resected specimens, this study investigated endothelial P-selectin (CD62, granular membrane protein-140) 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 immunoreactivity were detected that apparently corresponded ultrastructurally to stored and released distributions. Compared with the normal gut, there was a 3.7-fold increase of P-selectin immunoreactivity on veins (p < 0.0001), venules (p < 0.0001), and capillaries (p < 0.05) in the highly inflamed gut, without differences between Crohn's disease and ulcerative colitis. In the uninvolved gut, P-selectin expression was similar to that seen in normal controls, except for a focal increase of P-selectin in the vicinity of small lymphocyte aggregates. The dramatic upregulation of P-selectin in the inflamed tissue and its potential role in leucocyte trafficking support the concept of P-selectin blocking therapy for the control of active IBD.
Schürmann
G M
GM
Department of Histochemistry, Royal Postgraduate Medical School, London.
Bishop
A E
AE
Facer
P
P
Vecchio
M
M
Lee
J C
JC
Rampton
D S
DS
Polak
J M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins