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(Journal of Leukocyte Biology. 2002;72:56-64.)
© 2002 by Society for Leukocyte Biology

The role of P-selectin in experimental colitis as determined by antibody immunoblockade and genetically deficient mice

Meritxell Gironella^*, Meritxell Mollà^*, Azucena Salas^*, Antonio Soriano^*, Miquel Sans^*, Daniel Closa, Pablo Engel, Antonio Salas, Josep M. Piqué^* and Julián Panés^*

^* 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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