Mayadas T N, Mendrick D L, Brady H R, Tang T, Papayianni A, Assmann K J, Wagner D D, Hynes R O, Cotran R S
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Kidney Int. 1996 May;49(5):1342-9. doi: 10.1038/ki.1996.190.
P-selectin present on surfaces of activated endothelium and platelets mediates neutrophil-endothelial and neutrophilplatelet interactions. The role of P-selectin in vivo was examined in a model of acute passive anti-GBM nephritis in P-selectin-deficient and wild-type mice which was induced by intravenous injection of anti-GBM serum. There were two major differences between P-selectin-deficient and wild-type mice. Firstly, mutant mice had approximately two fold more glomerular PMNs and albuminuria than wild-type animals at the peak of neutrophil influx and proteinuria. Secondly, Lipoxin A4 (LXA4), an eicosanoid which inhibits leukocyte-endothelial adhesion in vitro, and is generated primarily by transcellular biosynthetic routes during P-selectin-mediated platelet-PMN interaction [1], was approximately 60% of wild type levels in nephritic kidneys of P-selectin-deficient mice. Injection of wild-type platelets into P-selectin-null mice restored LXA4 to wild-type levels. The corresponding PMN influx approximated PMN levels in wild-type mice receiving platelets but urine albuminuria remained higher. Although these two P-selectin-dependent events cannot be directly linked, our results point to the importance of considering both platelet and endothelial P-selectin in determining the cellular events in inflammation.
存在于活化内皮细胞和血小板表面的P-选择素介导中性粒细胞与内皮细胞以及中性粒细胞与血小板的相互作用。在P-选择素缺陷型和野生型小鼠的急性被动抗肾小球基底膜肾炎模型中，通过静脉注射抗肾小球基底膜血清诱导肾炎，研究了P-选择素在体内的作用。P-选择素缺陷型小鼠和野生型小鼠之间存在两个主要差异。首先，在中性粒细胞流入和蛋白尿达到峰值时，突变小鼠的肾小球多形核中性粒细胞（PMN）和蛋白尿比野生型动物多约两倍。其次，脂氧素A4（LXA4）是一种在体外抑制白细胞与内皮细胞黏附的类花生酸，主要在P-选择素介导的血小板与PMN相互作用过程中通过跨细胞生物合成途径产生[1]，在P-选择素缺陷型小鼠的肾炎肾脏中，其水平约为野生型水平的60%。将野生型血小板注射到P-选择素缺失的小鼠体内可使LXA4恢复到野生型水平。相应的PMN流入量接近接受血小板的野生型小鼠中的PMN水平，但尿蛋白水平仍然较高。虽然这两个依赖P-选择素的事件不能直接联系起来，但我们的结果表明，在确定炎症中的细胞事件时，考虑血小板和内皮细胞的P-选择素都很重要。
