Expression of intercellular adhesion molecule-1 on rat cardiac myocytes by monocyte chemoattractant protein-1.
OBJECTIVE
Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) on cardiac myocytes may be a critical step in cardiac inflammation associated with acute myocardial infarction and myocarditis. The aim of this study was to investigate the involvement of monocyte chemoattractant protein-1 (MCP-1), a homologue of mouse JE, in the neutrophil-myocyte adhesion in vitro.


METHODS
MCP-1/JE and ICAM-1 mRNA expression 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 1 alpha (100 U.ml-1), lipopolysaccharide (1 microgram.ml-1), or hypoxia (95% N2 + 5% CO2). In ELISA analysis, the expression of ICAM-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 was constitutively observed in myocytes, and the expression was markedly stimulated by exposure to MCP-1 with a peak elevation at 2 h. In adherence assay, MCP-1 stimulated the adhesion of rat neutrophils to rat cardiac myocytes, and this effect of MCP-1 was inhibited by an anti-ICAM-1 MAb.


CONCLUSIONS
These results suggest that cardiac myocytes produce 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.
Ban
K
K
Jichi Medical School, Tochigi, Japan.
Ikeda
U
U
Takahashi
M
M
Kanbe
T
T
Kasahara
T
T
Shimada
K
K
D000818:Animals; D015152:Blotting, Northern; D002448:Cell Adhesion; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1