Roles and relationship of macrophages and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the ischemic and reperfused rat heart

Reperfusion injury is a troublesome and unresolved problem in acute myocard ial infarction and is believed to be associated with inflammatory reactions in which various types of cells and cytokines participate, in particular, macrophages and monocyte chemoattractant protein-1 (MCP-1). We designed thi s study to clarify the role and relationship of macrophages and MCP-1 in is chemic and reperfused heart. The number and distribution of macrophages and MCP-1 messenger RNA (mRNA) in the ischemic and reperfused rat heart were e xamined with in situ hybridization and immunohistochemistry. Myocardial sam ples were obtained at several times. in situ hybridization was performed wi th digoxigenin-labeled antisense RNA probe for rat MCP-1 mRNA, and immunohi stochemistry was performed with antimacrophage antibody. Double staining wi th in situ hybridization and immunohistochemistry was also performed. The n umber of MCP-1 mRNA-positive cells increased after reperfusion and peaked a t 3 hours after reperfusion. Early infiltration of ischemic tissues by macr ophages was also observed at the time of the absence of an increase of MCP- 1 mRNA-positive cells, and this infiltration was not significantly accelera ted by reperfusion, but by ischemia itself. The numbers of both MCP-1 mRNA- positive cells and macrophages increased in the ischemic marginal region ov er time. From the result of double staining, and based on the cellular morp hology and the distribution, the majority of MCP-1 mRNA-positive cells appe ared to be activated macrophages. This suggests that macrophages may not be attracted to cardiac tissue only by MCP-1 and that MCP-1 may have some rol es other than attracting macrophages into ischemic heart. It also suggests that macrophages and MCP-1 may play an important role in reperfusion injury and that MCP-1 may be one of the key molecules of reperfusion injury. Thes e observations may contribute to the development of a new therapeutic appro ach to the prevention of reperfusion injury.