Weksler B B, Jaffe E A, Brower M S, Cole O F
Department of Medicine, Cornell University Medical College, New York, NY.
Blood. 1989 Oct;74(5):1627-34.
Polymorphonuclear leukocytes (PMN) when activated release products that can potentially injure endothelial cells or alter endothelial function. Exposure of cultured human umbilical vein endothelial cells to cathepsin G and elastase isolated from human PMN at concentrations reached in vivo (100 ng/mL to 10 micrograms/mL) selectively inhibited thrombin-induced prostacyclin production and the thrombin-induced rise in cytosolic free calcium ([Ca++]i) concentration. These proteases also blocked thrombin-induced release of arachidonic acid from prelabeled endothelial cells (EC). In contrast, induction of prostacyclin (PGI2) production by arachidonate, histamine, or the calcium ionophore A23187 was not altered by treatment of EC with these proteases. The effects of the proteases were concentration-dependent, were blocked by serum or serum protease inhibitors, and were reversed when the endothelial cells were further cultured for 24 hours in the absence of the proteases. Elastase, but not cathepsin G, also produced detachment of endothelial cells. Thus, the major leukocyte proteases selectively suppress thrombin-induced prostacyclin production by human vascular endothelial cells and may alter the hemostatic balance at sites of PMN activation.
多形核白细胞（PMN）激活后会释放可能损伤内皮细胞或改变内皮功能的产物。将培养的人脐静脉内皮细胞暴露于从人PMN中分离出的组织蛋白酶G和弹性蛋白酶，浓度达到体内水平（100 ng/mL至10 μg/mL）时，会选择性抑制凝血酶诱导的前列环素生成以及凝血酶诱导的胞质游离钙（[Ca++]i）浓度升高。这些蛋白酶还会阻断凝血酶诱导的预先标记的内皮细胞（EC）中花生四烯酸的释放。相比之下，用这些蛋白酶处理EC不会改变花生四烯酸、组胺或钙离子载体A23187诱导的前列环素（PGI2）生成。蛋白酶的作用具有浓度依赖性，可被血清或血清蛋白酶抑制剂阻断，并且当内皮细胞在无蛋白酶的情况下进一步培养24小时时作用会逆转。弹性蛋白酶而非组织蛋白酶G也会导致内皮细胞脱离。因此，主要的白细胞蛋白酶选择性抑制人血管内皮细胞凝血酶诱导的前列环素生成，并可能改变PMN激活部位的止血平衡。
