Hansen P R, Kharazmi A
Department of Medicine B (Division of Cardiology), University of Copenhagen, Denmark.
J Mol Cell Cardiol. 1994 Aug;26(8):1061-8. doi: 10.1006/jmcc.1994.1126.
The clinical benefit of streptokinase (SK) in the treatment of patients with acute myocardial infarction may be influenced by effects other than myocardial reperfusion per se. Polymorphonuclear leucocytes (PMNs) have been hypothesized to participate in the process of reperfusion injury in the postischemic myocardium. The purpose of the present study was therefore to investigate the effect of SK on human PMN function in vitro, and ex vivo in patients with acute myocardial infarction. SK was not in itself chemotactic to PMNs, and preincubation with SK did not alter the chemotactic response of PMNs to formyl-Met-Leu-Phe (FMLP) or zymosan-activated serum. However, incubation of fresh citrated plasma with SK resulted in the generation of chemotactic activity, and this effect was dependent on complement activation by SK. In experiments with PMNs from 20 health donors, preincubation of plasma and SK, followed by incubation with PMNs, primed the cells for enhanced chemiluminescence response to FMLP. The PMN priming by SK+plasma showed considerable interindividual variation, and was not mediated by a direct action of plasmin on PMNs. In 10 patients with acute myocardial infarction treated with SK, a reduction in superoxide production by PMNs was observed immediately following SK. The results suggest that SK modulates human PMN function in vivo, and these effects may influence the therapeutical value of this agent.
链激酶(SK)治疗急性心肌梗死患者的临床益处可能受到心肌再灌注本身以外的其他因素影响。据推测,多形核白细胞(PMN)参与缺血后心肌的再灌注损伤过程。因此,本研究的目的是调查SK在体外对人PMN功能的影响,以及在急性心肌梗死患者体内的影响。SK本身对PMN没有趋化作用,预先用SK孵育不会改变PMN对甲酰甲硫氨酰亮氨酰苯丙氨酸(FMLP)或酵母聚糖激活血清的趋化反应。然而,新鲜枸橼酸盐血浆与SK孵育会产生趋化活性,且这种作用依赖于SK对补体的激活。在对20名健康供体的PMN进行的实验中,血浆与SK预先孵育,然后与PMN孵育,会使细胞对FMLP的化学发光反应增强。SK+血浆对PMN的预激发表现出相当大的个体间差异,且不是由纤溶酶对PMN的直接作用介导的。在10名接受SK治疗的急性心肌梗死患者中,SK治疗后立即观察到PMN超氧化物生成减少。结果表明,SK在体内调节人PMN功能,这些作用可能会影响该药物的治疗价值。