(Circulation. 1999;99:1560-1566.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Endothelial Cytotoxicity Mediated by Serum Antibodies to Heat Shock Proteins of Escherichia coli and Chlamydia pneumoniae
Immune Reactions to Heat Shock Proteins as a Possible Link Between Infection and Atherosclerosis
From the Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck (M.M., B.M., G.S., Q.X., G.W.); Department of Neurology, University Clinic, Innsbruck (S.K., J.W.); and Institute for General and Experimental Pathology, University of Innsbruck, Medical School, Innsbruck, Austria (M.M., G.W.).
Correspondence to Dr Georg Wick, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria. E-mail IBA{at}oeaw.ac.at
Background—Growing evidence suggests that an immunological reaction against heat shock proteins (HSPs) may be involved in atherogenesis. Because HSPs show a high degree of amino acid sequence homology between different species, from prokaryotes to humans, we investigated the possibility of "antigenic mimicry" caused by an immunological cross-reaction between microorganisms and autoantigens.
Methods and Results—Serum antibodies against the Escherichia coli HSP (GroEL) and the 60-kDa chlamydial HSP (cHSP60) from subjects with atherosclerosis were purified by use of affinity chromatography. Western blot analyses and competitive ELISAs confirmed the cross-reaction of the eluted antibodies with human HSP60 and the bacterial counterparts. The cytotoxicity of anti-GroEL and anti-cHSP60 antibodies was determined on human endothelial cells labeled with 51Cr. A significant difference (40% versus 8%) was observed in the specific 51Cr release of heat-treated (42°C for 30 minutes) and untreated cells, respectively, in the presence of these anti-HSP antibodies and complement. This effect was blocked by addition of 100 µg/mL recombinant GroEL. In addition, seropositivity against specific non-HSP60 Chlamydia pneumoniae antigens is more prominent among high–anti-HSP titer sera than low-titer sera.
Conclusions—Serum antibodies against HSP65/60 cross-react with human HSP60, cHSP60, and GroEL; correlate with the presence of antibodies to C pneumoniae and endotoxin; and mediate endothelial cytotoxicity. These findings suggest that humoral immune reactions to bacterial HSPs, such as cHSP60 and GroEL, may play an important role in the process of vascular endothelial injury, which is believed to be a key event in the pathogenesis of atherosclerosis.
Key Words: stress • immunology • antibodies • C pneumoniae • atherosclerosis
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