REGULATION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IN ISCHEMIC AND REPERFUSED CANINE MYOCARDIUM
REGULATION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IN ISCHEMIC AND REPERFUSED CANINE MYOCARDIUM
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DOI：
10.1172/jci116729
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发表时间：
1993-09-01
影响因子：
15.9
通讯作者：
ANDERSON, DC
中科院分区：
文献类型：
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作者：
KUKIELKA, GL;HAWKINS, HK;ANDERSON, DC
先前的体外研究表明，细胞间粘附分子-1（ICAM-1）在犬中性粒细胞与犬颈静脉内皮细胞的粘附相互作用以及犬中性粒细胞对成人心肌细胞的细胞毒性中起重要作用。为了探讨ICAM-1在心肌炎症中的调节作用及其在心肌缺血和再灌注发病机制中的作用，在犬动物中进行了一系列体内和离体研究。全身给药的LPS引发ICAM-1 mRNA在几个组织，包括心肌，这表明增加心肌细胞闰盘上的ICAM-1染色。在缺血和再灌注过程中：（a）再灌注1小时内在缺血节段和再灌注24小时时在缺血和正常灌注节段中均发现ICAM-1 mRNA，（B）再灌注6小时时在缺血区心肌细胞中检测到ICAM-1表达，此后随着时间的推移，表达增加;（c）缺血后再灌注后1 ~ 24 h收集的（但非缺血前）心脏淋巴液可诱导犬颈静脉内皮细胞和心肌细胞ICAM-1 mRNA、ICAM-1表达和ICAM-1依赖性中性粒细胞粘附，细胞因子活性在1 h时达到峰值;（d）仅在缺血区域检测到中性粒细胞的血管外定位，并且与再灌注1小时内具有高水平ICAM-1的内皮相关;此后浸润增加，与心肌节段中ICAM-1 mRNA水平的增加和心肌细胞上ICAM-1表达水平的增加相关。这些发现为ICAM-1在缺血再灌注犬心肌中的炎症调节提供了第一个直接证据。支持ICAM-1参与嗜中性粒细胞介导的心肌损伤的假说。
Previous studies in vitro have shown an important role for intercellular adhesion molecule-1 (ICAM-1) in adherence interactions of canine neutrophils with canine jugular vein endothelial cells and in cytotoxicity of canine neutrophils for adult cardiac myocytes. To evaluate the regulation of ICAM-1 in myocardial inflammation and its role in the pathogenesis of myocardial ischemia and reperfusion, a series of in vivo and ex vivo studies were performed in canine animals. Systemic administration of LPS elicited ICAM-1 mRNA in several tissues, including myocardium, which demonstrated increasing ICAM-1 staining on intercalated discs of cardiac myocytes. In ischemia and reperfusion protocols: (a) ICAM-1 mRNA was found in ischemic segments within 1 h of reperfusion and in both ischemic and normally perfused segments by 24 h of reperfusion; (b) expression of ICAM-1 was detected in cardiac myocytes in the ischemic region by 6 h of reperfusion; increased expression was seen thereafter as a function of time; (c) postischemic (but not preischemic) cardiac lymph collected at intervals from 1 to 24 h after reperfusion elicited ICAM-1 mRNA, ICAM-1 expression, and ICAM-1-dependent neutrophil adhesion in canine jugular vein endothelial cells and in cardiac myocytes with peak cytokine activity seen by 1 h; (d) extravascular localization of neutrophils was detected in ischemic areas only, and was associated with endothelium bearing high levels of ICAM-1 within 1 h of reperfusion; infiltration increased thereafter in association with increasing levels of ICAM-1 mRNA in myocardial segments and increasing levels of ICAM-1 expression on cardiac myocytes. These findings provide the first direct evidence for inflammatory regulation of ICAM-1 in ischemic and reperfused canine myocardium. They support the hypothesis that ICAM-1 participates in neutrophil-mediated myocardial damage.