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 autoantibodies to bacterial hsp65 crossreacting with human hsp60 (anti-hsp60 autoantibodies), myocardial infarction entails decreased humoral immune response to hsp65. We previously hypothesized that myocardial ischemia and subsequent 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 study, 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 enzymes. Myocardial hsp60 expression was induced up to threefold in response to 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 recognized by anti-hsp65 serum antibodies and induced proliferation of hsp65-specific T cells. When hsp60-containing coronary eluate was reinjected into an hsp65-primed rat, both humoral and cellular hsp65-immune responses were strongly downregulated.


CONCLUSIONS
Our findings demonstrate the release of highly immunogenic and crossreactive hsp60 into the circulation in response to myocardial ischemia and myocardiocyte injury.
Schett
G
G
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
Metzler
B
B
Kleindienst
R
R
Amberger
A
A
Recheis
H
H
Xu
Q
Q
Wick
G
G
D000818:Animals; D000917:Antibody Formation; D018834:Chaperonin 60 / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D017202:Myocardial Ischemia / Q000276:immunology / Q000378:metabolism*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology
D018834:Chaperonin 60