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

First Author  Gironella M Year  2002
Journal  J Leukoc Biol Volume  72
Issue  1 Pages  56-64
PubMed ID  12101263 Mgi Jnum  J:124457
Mgi Id  MGI:3721732 Citation  Gironella M, et al. (2002) The role of P-selectin in experimental colitis as determined by antibody immunoblockade and genetically deficient mice. J Leukoc Biol 72(1):56-64
abstractText  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.
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