Immune effector mechanisms in myocardial pathologies.
It is now well established that immune effector mechanisms contribute to cardiac dysfunction in several heart diseases, including myocarditis and the associated dilated cardiomyopathy, heart transplant rejection and Chagas' disease. These and other pathologies, in which cellular immunity plays an important role, contribute to morbidity and mortality world-wide. As a result of numerous studies performed in this exciting field, two major mechanisms of lymphocytotoxicity have been proposed: a secretory mechanism in which perforin and granzymes are key players, and a non-secretory mechanism involving Fas/FasL activation. While the common notion is that CTL-myocyte interaction, perforin- or Fas-based, inevitably results in target cell apoptotic death, the objective of this review is to consider the concept of non-apoptotic consequences of CTL-target cell interaction. It is proposed that depending on the myocyte status as well as on the fine balance between pro- and anti-apoptotic factors, CTL-myocyte interaction may result in a non-apoptotic, potentially reversible sustained damage to the myocytes, thus contributing to immune-mediated cardiac dysfunction.
Binah
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Rappaport Institute, P.O. Box 9697, Haifa 31096, Israel.
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium