Gironella Meritxell, Mollà Meritxell, Salas Azucena, Soriano Antonio, Sans Miquel, Closa Daniel, Engel Pablo, Salas Antonio, Piqué Josep M, Panés Julián
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.
J Leukoc Biol. 2002 Jul;72(1):56-64.
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.
我们评估了P-选择素基因的基因敲除与P-选择素的功能性免疫阻断相比，对葡聚糖硫酸钠诱导的小鼠结肠炎中白细胞募集和疾病进程的影响。与对照抗体处理的野生型（WT）小鼠相比，用抗P-选择素抗体处理的WT小鼠和P-选择素基因敲除（P-selectin(-/-)）小鼠的结肠小静脉中白细胞滚动和黏附显著减少，临床和病理结肠炎评分降低。这些降低在抗P-选择素处理的小鼠中比在P-selectin(-/-)小鼠中更明显。在结肠内皮中，WT小鼠和P-selectin(-/-)小鼠中细胞间黏附分子-1（ICAM-1）的上调相似，但后者组中血管细胞黏附分子-1（VCAM-1）的上调显著更高。仅在P-selectin(-/-)结肠炎小鼠中肺白细胞浸润和VCAM-1表达增加。仅在P-selectin(-/-)小鼠中观察到死亡。因此，P-选择素功能的缺失改善了结肠炎，但这种保护在P-selectin(-/-)小鼠中减弱，可能是由于涉及上调其他黏附分子（如VCAM-1）的补偿机制。
