Kumar A G, Ballantyne C M, Michael L H, Kukielka G L, Youker K A, Lindsey M L, Hawkins H K, Birdsall H H, MacKay C R, LaRosa G J, Rossen R D, Smith C W, Entman M L
Methodist Hospital, DeBakey Heart Center, Department of Medicine, Houston, TX, USA.
Circulation. 1997 Feb 4;95(3):693-700. doi: 10.1161/01.cir.95.3.693.
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.
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 microns in diameter.
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.
心肌梗死后的愈合表现为梗死区域有巨噬细胞存在。由于单核细胞流入增加被认为是再灌注后愈合改善的潜在机制，我们希望研究再灌注期间单核细胞趋化蛋白-1（MCP-1）的诱导情况。
从犬颈静脉内皮细胞（CJVEC）文库中克隆出MCP-1的cDNA，其推导的氨基酸序列与人类MCP-1有78%的同源性。在缺血1小时及不同再灌注时间后，从对照和缺血节段获取心肌样本；从心肌样本中分离总RNA，并用犬MCP-1的cDNA探针进行检测。MCP-1 mRNA的诱导仅在再灌注的第一小时内出现在先前缺血的节段，在3小时达到峰值，并在再灌注的前两天持续存在。在没有再灌注的情况下，未观察到明显的MCP-1诱导。缺血（而非缺血前）心脏淋巴液和重组人肿瘤坏死因子-α均可在CJVEC中诱导MCP-1。3小时时，通过免疫染色在浸润细胞和小静脉（而非动脉）内皮上鉴定出MCP-1。相比之下，原位杂交显示MCP-1 mRNA局限于直径为10至70微米的小静脉内皮。
再灌注后立即在特定类型的小静脉内皮中诱导MCP-1 mRNA。MCP-1的诱导局限于已再灌注的先前缺血区域。我们认为MCP-1在再灌注心肌中的单核细胞迁移中起重要作用。
