EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1 ON RAT CARDIAC MYOCYTES BY MONOCYTE CHEMOATTRACTANT PROTEIN-1

Objective: Cytokine induction of intercellular adhesion molecule-1 (IC AM-1) on cardiac myocytes may be a critical step in cardiac inflammati on associated with acute myocardial infarction and myocarditis. The ai m of this study was to investigate the involvement of monocyte chemoat tractant protein-1 (MCP-1), a homologue of mouse JE, in the neutrophil -myocyte adhesion in vitro. Methods: MCP-1/JE and ICAM-1 mRNA expressi on in cultured neonatal rat cardiac myocytes was evaluated by northern blot analysis. ICAM-1 molecule content on myocytes was determined by ELISA. For adherence assay, myocytes and neutrophils were co-incubated and the number of bounded neutrophils was counted. Results: MCP-1/JE transcripts were not clearly observed in cultured neonatal rat cardiac myocytes; however, its transcripts were clearly detected by exposure to interleukin la (100 U.ml(-1)), lipopolysaccharide (1 mu g.ml(-1)), or hypoxia (95% N-2 + 5% CO2). In ELISA analysis, the expression of IC AM-1 molecules on cardiac myocytes was significantly stimulated by MCP -1 in a dose dependent manner, and the effect of MCP-1 was observed as early as at 6 h. In northern blot analysis, ICAM-1 mRNA expression wa s constitutively observed in myocytes, and the expression was markedly stimulated by exposure to MCP-1 with a peak elevation at 2 h. In adhe rence assay, MCP-1 stimulated the adhesion of rat neutrophils to rat c ardiac myocytes, and this effect of MCP-1 was inhibited by an anti-ICA M-1 MAb. Conclusions: These results suggest that cardiac myocytes prod uce MCP-1, which could in turn promote the adhesion of neutrophils to myocytes via ICAM-1 expression, suggesting the involvement of MCP-1 in cardiac inflammation associated with acute myocardial infarction and myocarditis