title: The role of P-selectin in experimental colitis as determined by antibody immunoblockade and genetically deficient mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gironella
authors.forename: Meritxell
authors.initials: M
authors.lastname: Mollà
authors.forename: Azucena
authors.initials: A
authors.lastname: Salas
authors.forename: Antonio
authors.initials: A
authors.lastname: Soriano
authors.forename: Miquel
authors.initials: M
authors.lastname: Sans
authors.forename: Daniel
authors.initials: D
authors.lastname: Closa
authors.forename: Pablo
authors.initials: P
authors.lastname: Engel
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
authors.forename: Josep M
authors.initials: JM
authors.lastname: Piqué
authors.forename: Julián
authors.initials: J
authors.lastname: Panés
mesh_terms: 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
chemical_list: D000906:Antibodies; D015815:Cell Adhesion Molecules; D019007:P-Selectin