Kilgore K S, Park J L, Tanhehco E J, Booth E A, Marks R M, Lucchesi B R
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626, USA.
J Mol Cell Cardiol. 1998 Jan;30(1):75-85. doi: 10.1006/jmcc.1997.0573.
Neutrophil accumulation and activation of the complement system with subsequent deposition of the cytolytic membrane attack complex (MAC) have been implicated in the pathogenesis of myocardial ischemia/reperfusion injury. The MAC, when present in high concentrations, promotes target cell lysis. However, relatively little is known about the potential modulatory role of sublytic concentrations of the MAC on nucleated cell function in vivo. In vitro studies demonstrated that the MAC regulates cell function by promoting the expression of pro-inflammatory mediators, including adhesion molecules and pro-inflammatory cytokines. We examined, using C6-deficient and C6-sufficient rabbits, the regulatory role of the MAC in mediating IL-8 expression and subsequent neutrophil recruitment in the setting of myocardial ischemia/reperfusion injury. C6-deficient and C6-sufficient rabbits were subjected to 30 min of regional myocardial ischemia followed by a period of reperfusion. In addition to a significant reduction in myocardial infarct size in C6-deficient animals, analysis of myocardial tissue demonstrated a decrease in neutrophil influx into the infarcted region. The reduction in neutrophil influx correlated with the decreased expression of the neutrophil chemotactic cytokine IL-8, as determined by ELISA and immunohistochemical analysis. The results derived from this study provide evidence that the MAC has an important function in mediating the recruitment of neutrophils to the reperfused myocardium through the local induction of IL-8.
中性粒细胞的聚集以及补体系统的激活，随后细胞溶解性膜攻击复合物（MAC）的沉积，都与心肌缺血/再灌注损伤的发病机制有关。当MAC浓度很高时，会促进靶细胞溶解。然而，关于体内亚溶解浓度的MAC对有核细胞功能的潜在调节作用，人们了解得相对较少。体外研究表明，MAC通过促进包括黏附分子和促炎细胞因子在内的促炎介质的表达来调节细胞功能。我们使用C6缺陷和C6充足的兔子，研究了MAC在心肌缺血/再灌注损伤情况下介导白细胞介素-8（IL-8）表达及随后中性粒细胞募集的调节作用。C6缺陷和C6充足的兔子经历30分钟的局部心肌缺血，随后进行一段时间的再灌注。除了C6缺陷动物的心肌梗死面积显著减小外，对心肌组织的分析表明，梗死区域中性粒细胞的流入减少。中性粒细胞流入的减少与中性粒细胞趋化细胞因子IL-8表达的降低相关，这是通过酶联免疫吸附测定（ELISA）和免疫组织化学分析确定的。这项研究的结果提供了证据，表明MAC在通过局部诱导IL-8介导中性粒细胞向再灌注心肌募集方面具有重要作用。
