Intestinal inflammation in adhesion molecule-deficient mice: an assessment of P-selectin alone and in combination with ICAM-1 or E-selectin.
Biopsy specimens from patients with inflammatory bowel disease have demonstrated an up-regulation of P-selectin, suggesting a role for P-selectin in intestinal inflammation. We examined the role of P-selectin in experimental intestinal inflammation using mice deficient in P-selectin alone or in combination with either ICAM-1 or E-selectin. Colitis was induced using acetic acid or trinitrobenzene sulfonic acid (TNBS). Damage scores and neutrophil infiltration 24 h post acetic acid were not different between wild-type and P-selectin- or P-selectin/ICAM-1-deficient mice, whereas P/E-selectin-deficient mice had enhanced leukocyte recruitment and damage. At 72 h an attenuation in damage scores and a slight decrease in neutrophil infiltration was observed in the P- and P/ICAM-deficient animals. The P/E-selectin-deficient mice maintained enhanced leukocyte recruitment and damage. In wild-type mice P-selectin expression was elevated 48 and 72 h post acetic acid-induced inflammation. Surprisingly, P-selectin or P-selectin/ICAM-1 deficiency did not improve the inflammation induced by TNBS over 7 days. In fact, increased mortality was observed. Anti-adhesion therapy may play only a limited, beneficial role and often a detrimental role in intestinal inflammation.
Immunology Research Group, University of Calgary, Alberta, Canada.
D M
DM
McCafferty
C W
CW
Smith
D N
DN
Granger
P
P
Kubes
D000085:Acetates; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000378:metabolism; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid
D000085:Acetates; D019040:E-Selectin; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D014302:Trinitrobenzenesulfonic Acid