Myocardial injury leads to a release of heat shock protein (hsp) 60 and a suppression of the anti-hsp65 immune response

Objective: While atherosclerosis is associated with high titers of autoanti bodies to bacterial hsp65 crossreacting with human hsp60 (anti-hsp60 autoan tibodies), myocardial infarction entails decreased humoral immune response to hsp65. We previously hypothesized that myocardial ischemia and subsequen t infarction not only induce myocardial hsp60 expression, but also trigger release of myocardial hsp60 into the circulation, influencing the systemic hsp immune response via immune complex formation. Methods: In the present s tudy, organ culture of rat hearts under circulatory arrest provided a model of myocardiocyte injury due to ischemia. Results: Reperfusion of ischemic hearts confirmed the occurrence of myocardial injury by a rise of heart enz ymes. Myocardial hsp60 expression was induced up to threefold in response t o ischemia, and most of hsp60 expression was localized to the muscle fibers . Analysis of coronary eluate revealed release of hsp60 from myocardium. In addition, hsp60-containing, but not hsp60-free, coronary eluate was recogn ized by anti-hsp65 serum antibodies and induced proliferation of hsp65-spec ific T cells. When hsp60-containing coronary eluate was reinjected into an hsp65-primed rat, both humoral and cellular hsp65-immune responses were str ongly downregulated. Conclusion: Our findings demonstrate the release of hi ghly immunogenic and crossreactive hsp60 into the circulation in response t o myocardial ischemia and myocardiocyte injury. (C) 1999 Elsevier Science B .V. All rights reserved.