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. 1993 Apr;91(4):1327–1336. doi: 10.1172/JCI116333

Expression of intercellular adhesion molecule-1 in murine hearts with acute myocarditis caused by coxsackievirus B3.

Y Seko 1, H Matsuda 1, K Kato 1, Y Hashimoto 1, H Yagita 1, K Okumura 1, Y Yazaki 1
PMCID: PMC288103  PMID: 8097205

Abstract

A cell-mediated autoimmune mechanism has been strongly implicated in the pathogenesis of viral myocarditis. Using a murine model of myocarditis caused by coxsackievirus B3 (CVB3), we previously reported that the heart is infiltrated first by natural killer cells, which express a cytolytic factor, perforin, and then by activated T cells. This action may play an important role in the pathogenesis of the observed myocardial cell damage. Cell-cell contact and adhesion is required in immune responses, and intercellular adhesion molecule-1 (ICAM-1), which is a ligand for lymphocyte function-associated antigen-1 (LFA-1), plays an important role in this process. To investigate the essential role of the ICAM-1/LFA-1 pathway in the cell-mediated cytotoxicity involved in viral myocarditis, we examined by immunofluorescence the expression of ICAM-1 in murine hearts with acute myocarditis caused by CVB3. We also evaluated the induction of ICAM-1 in cultured cardiac myocytes treated with cytokines by immunofluorescence and Northern blot hybridization. Furthermore, we analyzed the effects of in vivo administration of anti-ICAM-1 mAbs on the inflammation associated with acute viral myocarditis. We found that CVB3-induced murine acute myocarditis resulted in enhanced expression of ICAM-1 in myocardial cells. The expression of ICAM-1 in myocardial cells could be induced in vitro by IFN-gamma and TNF-alpha, which were shown to be synthesized by the infiltrating cells. In vivo treatment with F(ab')2 fragments of an anti-ICAM-1 mAb significantly reduced the myocardial inflammation induced by CVB3. These data strongly suggest that the expression of ICAM-1 in myocardial cells plays a critical role in the cell-mediated cytotoxicity involved in acute viral myocarditis.

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Selected References

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