Integrins and Monocyte Migration to the Ischemic Myocardium

AIMS: Characterize mononuclear cell migration after acute-myocardial infarction (MI). MATERIAL AND METHODS: Male Lewis rats underwent a left thoracotomy and ligation of the left anterior descending coronary artery (MI group). Control animals underwent thoracotomy without ligation (Sham group). Animals were sacrificed at 0, 2, 4, or 24 hr after the onset of ischemia. Leukocyte migration was assessed using isolated and In(111) labeled mononuclear cells (injected at the onset of ischemia) and gamma-count determined at 24 hours. Inhibition of migration was evaluated with monoclonal anti alpha4 and/or beta2 antibodies. RESULTS: Serum troponin was significantly elevated in animals with MI as compared with Sham (p = .017). Labeled mononuclear cell migration was five-fold higher in MI-treated animals than in Sham (p = .006). ED-1 positive mononuclear cells were confirmed in the left myocardium after 24 hr of ischemia. MCP-1 mRNA was significantly elevated in the left myocardium at 2 hr and 4 hr and peaked at 24 hr (p <.05). In addition, alpha4 integrin blockade inhibited labeled mononuclear cell migration by 22%. Blockade of beta2 integrin inhibited mononuclear cell migration by 48%, while the combined alpha4+beta2 blockade resulted in 59% inhibition of labeled mononuclear cell migration compared with treatment with isotype control antibody (p = .001). CONCLUSIONS: Significant ED1+ mononuclear cell migration within 24 hr of MI correlated with peak MCP-1 mRNA. Monoclonal antibody blockade suggested that early mononuclear cell migration is dependent only in part on alpha4 and beta2 integrins.