* Department of Gastroenterology, Institut de Malalties Digestives, and
Liver Unit, Hospital Clínic, and
Department of Medical Bioanalysis, IIBB-CSIC, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain; and
Department of Pathology, Hospital Mutua of Terrassa, Barcelona, Spain
Correspondence: Julián Panés, Gastroenterology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. E-mail: panes{at}medicina.ub.es
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.
Key Words: adhesion molecules • inflammatory bowel disease • endothelium • leukocyte
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