INDUCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN THE SMALL VEINS OFTHE ISCHEMIC AND REPERFUSED CANINE MYOCARDIUM

Background Healing after myocardial infarction is characterized by the presence of macrophages in the infarcted area. Since augmented monocy te influx has been implicated as a potential mechanism for improved he aling after reperfusion, we wished to study the induction of monocyte chemoattractant protein-1 (MCP-1) during reperfusion. Methods and Resu lts The cDNA for MCP-1 was cloned from a canine jugular vein endotheli al cell (CJVEC) library and exhibited 78% identity with the deduced am ino acid sequence of human MCP-1. Samples of myocardium were taken fro m control and ischemic segments after 1 hour of ischemia and various t imes of reperfusion; total RNA was isolated from myocardial samples an d probed with a cDNA probe for canine MCP-1. Induction of MCP-1 mRNA o ccurred only in previously ischemic segments within the first hour of reperfusion, peaked at 3 hours, and persisted throughout the first 2 d ays of reperfusion. In the absence of reperfusion, no significant MCP- 1 induction was seen. Both ischemic (but not preischemic) cardiac lymp h and human recombinant TNF-alpha induced MCP-1 in CJVECs MCP-1 was id entified by immunostaining on infiltrating cells and venular (but not arterial) endothelium by 3 hours. In contrast, in situ hybridization s howed MCP-1 mRNA to be confined to the endothelium of small veins (ven ules) 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 r eperfusion. MCP-1 induction is confined to the previously ischemic are a that has been reperfused. We suggest a significant role for MCP-1 in monocyte trafficking in the reperfused myocardium.