Induction of monocyte chemoattractant protein-1 in the small veins of the ischemic and reperfused canine myocardium
Induction of monocyte chemoattractant protein-1 in the small veins of the ischemic and reperfused canine myocardium
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DOI：
10.1161/01.cir.95.3.693
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发表时间：
1997-02-04
期刊：
影响因子：
37.8
通讯作者：
Entman, ML
中科院分区：
文献类型：
--
作者：
Kumar, AG;Ballantyne, CM;Entman, ML
背景心肌梗死后的愈合以梗死区巨噬细胞的存在为特征。由于增加单核细胞内流是改善再灌注后愈合的潜在机制，我们希望研究再灌注过程中单核细胞趋化蛋白-1(MCP-1)的诱导。方法和结果从犬颈静脉内皮细胞(CJVEC)文库中克隆了MCP-1的cDNA，并与人MCP-1的推导氨基酸序列进行了78%的同源性分析。分别于缺血1h和再灌注不同时间取对照组和缺血节段心肌标本，提取总RNA，用犬MCP-1基因探针进行探针检测。单核细胞趋化蛋白-1mRNA的表达仅在再灌流后1小时内出现，在再灌流后3小时达到高峰，并持续到再灌流的前2天。在无再灌流的情况下，未见明显的MCP-1诱导。缺血(但不是缺血前)心脏淋巴和人重组肿瘤坏死因子-α诱导的CJVECs MCP-1在3h后通过免疫组织化学染色对浸润性细胞和静脉(但不是动脉)内皮细胞进行鉴定。而原位杂交显示MCP-1mRNA仅定位于直径10~70微米的小静脉(小静脉)内皮细胞。单核细胞趋化蛋白-1的诱导仅限于先前已再灌流的缺血区。我们认为单核细胞趋化蛋白-1在再灌流心肌单核细胞转运中起重要作用。
Background Healing after myocardial infarction is characterized by the presence of macrophages in the infarcted area. Since augmented monocyte influx has been implicated as a potential mechanism for improved healing after reperfusion, we wished to study the induction of monocyte chemoattractant protein-1 (MCP-1) during reperfusion.Methods and Results The cDNA for MCP-1 was cloned from a canine jugular vein endothelial cell (CJVEC) library and exhibited 78% identity with the deduced amino acid sequence of human MCP-1. Samples of myocardium were taken from control and ischemic segments after 1 hour of ischemia and various times of reperfusion; total RNA was isolated from myocardial samples and probed with a cDNA probe for canine MCP-1. Induction of MCP-1 mRNA occurred only in previously ischemic segments within the first hour of reperfusion, peaked at 3 hours, and persisted throughout the first 2 days of reperfusion. In the absence of reperfusion, no significant MCP-1 induction was seen. Both ischemic (but not preischemic) cardiac lymph and human recombinant TNF-alpha induced MCP-1 in CJVECs MCP-1 was identified by immunostaining on infiltrating cells and venular (but not arterial) endothelium by 3 hours. In contrast, in situ hybridization showed MCP-1 mRNA to be confined to the endothelium of small veins (venules) 10 to 70 mu m in diameter.Conclusions MCP-1 mRNA is induced in the endothelium of a specific class of small veins immediately after reperfusion. MCP-1 induction is confined to the previously ischemic area that has been reperfused. We suggest a significant role for MCP-1 in monocyte trafficking in the reperfused myocardium.