Reperfusion-induced leukocyte infiltration: role of elastase.
Reperfusion-induced leukocyte infiltration: role of elastase.
复制标题
DOI：
10.1152/ajpheart.1990.259.2.h390
复制
发表时间：
1990-08
期刊：
影响因子：
--
通讯作者：
B. Zimmerman;D. Granger
中科院分区：
文献类型：
--
作者：
B. Zimmerman;D. Granger
已知多态性白细胞在经受缺血和再灌注的组织中积聚。对内皮细胞单层的研究表明，弹性蛋白酶的有限释放通过基底膜降解在促炎介质引起的白细胞渗出和外渗中起重要作用。因此，本研究的目的是确定弹性蛋白酶在与缺血肠再灌注相关的白细胞浸润中的作用。在一系列实验中，猫小肠经受3小时的缺血（血流量降低至基线的20%）和1小时的再灌注。通过测量基线、缺血和再灌注期间获得的粘膜活检组织中的髓过氧化物酶活性来定量神经元的蓄积。用弹性蛋白酶抑制剂Eglin C和L658，758中的任一种预处理显著减弱了由再灌注而不是由缺血本身诱导的中性粒细胞浸润。在另一系列的实验中，白细胞粘附和外渗进行监测猫肠系膜静脉缺血和再灌注1小时。用L658，758预处理显著减弱了再灌注诱导的白细胞粘附和外渗率的增加，白细胞外渗率的降低比例更大。这些结果表明，弹性蛋白酶的释放是一个重要的因素，再灌注诱导的中性粒细胞浸润。
Polymorphonuclear leukocytes are known to accumulate in tissues subjected to ischemia and reperfusion. Studies on endothelial cell monolayers suggest that limited release of elastase plays an important role, via basement membrane degradation, in the leukocyte diapedesis and extravasation elicited by proinflammatory mediators. Thus the objective of this study was to define the role of elastase in the leukocyte infiltration associated with reperfusion of the ischemic bowel. In one series of experiments the cat small intestine was subjected to 3 h of ischemia (blood flow reduced to 20% of base line) and 1 h of reperfusion. Neutrophil accumulation was quantified by measurement of tissue myeloperoxidase activity in mucosal biopsies obtained during base-line, ischemic, and reperfusion periods. Pretreatment with either of the elastase inhibitors Eglin C and L658,758 significantly attenuated the neutrophil infiltration induced by reperfusion but not by ischemia per se. In another series of experiments, leukocyte adherence and extravasation were monitored in cat mesenteric venules subjected to 1 h of ischemia and reperfusion. Pretreatment with L658,758 significantly attenuated the increased rates of leukocyte adherence and extravasation induced by reperfusion, with a proportionately greater reduction in leukocyte extravasation rate. These results indicate that elastase release is an important factor in reperfusion-induced neutrophil infiltration.