Antibodies against human heat-shock protein (hsp) 60 and mycobacterial hsp65 differ in their antigen specificity and complement-activating ability.
Although complement activation appears to have an important role both in the early and late phases of atherosclerosis, the exact mechanism of the initiation of this activation is still unknown. Since injuries of the endothelial cells are known to result in increased stress-protein expression we tested the complement-activating ability of recombinant human 60 kDa heat-shock protein (hsp60). Human hsp60 was found to activate the complement system in normal human serum in a dose-dependent manner. Activation took place through the classical pathway. The lack of complement activation in agammaglobulinemic serum indicates that the classical pathway is triggered by anti-hsp60 antibodies. Hsp60 activated complement in the sera of 74 patients with coronary heart disease as well, and a strong positive correlation (r = 0.459, P < 0.0001) was found between the extent of complement activation and the level of anti-hsp60 IgG antibodies but there was no correlation to the level of anti-hsp65 IgG antibodies. Further distinction between anti-hsp60 and anti-hsp65 antibodies was obtained from competitive ELISA experiments: binding of anti-hsp60 antibodies to hsp60-coated plates was inhibited only by recombinant hsp60 and vice versa. Our present findings indicate that anti-hsp60 and anti-hsp65 antibodies are distinct, showing only partial cross-reactivity. Since complement activation plays an important role in the development of atherosclerosis and the levels of complement-activating anti-hsp60 antibodies are elevated in atherosclerosis-related diseases, our present findings may have important pathological implications.
Prohászka
Z
Z
Third Department of Medicine, Semmelweis University of Medicine, Budapest, Hungary.
Duba
J
J
Lakos
G
G
Kiss
E
E
Varga
L
L
Jánoskuti
L
L
Császár
A
A
Karádi
I
I
Nagy
K
K
Singh
M
M
Romics
L
L
Füst
G
G
D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins; D018834:Chaperonin 60 / Q000276:immunology*; D018833:Chaperonins / Q000276:immunology*; D002675:Child, Preschool; D003171:Complement Pathway, Classical / Q000276:immunology*; D003327:Coronary Disease / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D007074:Immunoglobulin G; D011994:Recombinant Proteins; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins