The role of P-selectin in experimental colitis as determined by antibody immunoblockade and genetically deficient mice.
We assessed the effects of genetic ablation of the P-selectin gene in comparison with functional immunoblockade of P-selectin on leukocyte recruitment and the course of disease in dextran sulfate sodium-induced colitis in mice. Compared with control antibody-treated wild-type (WT) mice, WT mice treated with anti-P-selectin antibody and P-selectin(-/-) mice had significantly decreased leukocyte rolling and adhesion in colonic venules and reduced clinical and pathological colitis scores. These reductions were more pronounced in anti-P-selectin-treated than in P-selectin(-/-) mice. In colonic endothelium, up-regulation of ICAM-1 was similar in WT and P-selectin(-/-) mice, but VCAM-1 up-regulation was significantly higher in the latter group. Lung leukocyte infiltration and VCAM-1 expression were increased only in P-selectin(-/-) colitic mice. Mortality was observed only in P-selectin(-/-) mice. Therefore, ablation of P-selectin function ameliorates colitis, but this protection is attenuated in P-selectin(-/-) mice, probably due to compensatory mechanisms that involve up-regulation of other adhesion molecules such as VCAM-1.
Gironella
Meritxell
M
Department of Gastroenterology, Institut de Malalties Digestives, IIBB-CSIC, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Villaroel 170, 08036 Barcelona, Spain.
Mollà
Meritxell
M
Salas
Azucena
A
Soriano
Antonio
A
Sans
Miquel
M
Closa
Daniel
D
Engel
Pablo
P
Salas
Antonio
A
Piqué
Josep M
JM
Panés
Julián
J
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000098:blood supply / Q000276:immunology; D004730:Endothelium, Vascular / Q000502:physiology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016019:Survival Analysis; D014699:Venules / Q000166:cytology / Q000502:physiology
D000906:Antibodies; D015815:Cell Adhesion Molecules; D019007:P-Selectin