International Immunology, Vol. 11, No. 9, 1363-1370,
September 1999
© 1999 Japanese Society for Immunology
Antibodies against human heat-shock protein (hsp) 60 and mycobacterial hsp65 differ in their antigen specificity and complement-activating ability
1 Third Department of Medicine, Semmelweis University of Medicine, Budapest, Hungary
2 Research Group of Metabolism, Genetics and Immunology, Hungarian Academy of Sciences, Budapest, Hungary
3 National Institute of Cardiology, Budapest, Hungary
4 Third Department of Medicine, University Medical School of Debrecen, Debrecen, Hungary
5 National Institute of Haematology and Immunology, Budapest, Hungary
6 Child Health Center, County Hospital Miskolc, Miskolc, Hungary
7 German National Research Center for Biotechnology, 38124 Braunschweig, Germany
Correspondence to: : Z. Prohászka, Kútvölgyi út 4, Budapest 1125, Hungary
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.
Keywords: anti-hsp60 antibodies, anti-hsp65 antibodies, atherosclerosis, classical pathway, complement activation, human heat-shock protein 60, mycobacterial heat-shock protein 65
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  X. Zhang, M.-A. He, L. Cheng, L. Zhou, H. Zeng, J. Wang, F. Wang, Y. Chen, F. B. Hu, and T. Wu Joint Effects of Antibody to Heat Shock Protein 60, Hypertension, and Diabetes on Risk of Coronary Heart Disease in Chinese Clin. Chem., June 1, 2008; 54(6): 1046 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Udvarnoki, L. Cervenak, K. Uray, F. Hudecz, I. Kacskovics, R. Spallek, M. Singh, G. Fust, and Z. Prohaszka Antibodies against C-Reactive Protein Cross-React with 60-Kilodalton Heat Shock Proteins Clin. Vaccine Immunol., April 1, 2007; 14(4): 335 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A G Pockley and J Frostegard Heat shock proteins in cardiovascular disease and the prognostic value of heat shock protein related measurements Heart, September 1, 2005; 91(9): 1124 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Uray, F. Hudecz, G. Fust, and Z. Prohaszka Comparative analysis of linear antibody epitopes on human and mycobacterial60-kDa heat shock proteins using samples of healthy blood donors Int. Immunol., October 1, 2003; 15(10): 1229 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Campisi and M. Fleshner Role of extracellular HSP72 in acute stress-induced potentiation of innate immunity in active rats J Appl Physiol, January 1, 2003; 94(1): 43 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Veres, G. Fust, M. Smieja, M. McQueen, A. Horvath, Q. Yi, A. Biro, J. Pogue, L. Romics, I. Karadi, et al. Relationship of Anti-60 kDa Heat Shock Protein and Anti-Cholesterol Antibodies to Cardiovascular Events Circulation, November 26, 2002; 106(22): 2775 - 2780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xu Role of Heat Shock Proteins in Atherosclerosis Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1547 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Burian, Z. Kis, D. Virok, V. Endresz, Z. Prohaszka, J. Duba, K. Berencsi, K. Boda, L. Horvath, L. Romics, et al. Independent and Joint Effects of Antibodies to Human Heat-Shock Protein 60 and Chlamydia pneumoniae Infection in the Development of Coronary Atherosclerosis Circulation, March 20, 2001; 103(11): 1503 - 1508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhu, A. A. Quyyumi, D. Rott, G. Csako, H. Wu, J. Halcox, and S. E. Epstein Antibodies to Human Heat-Shock Protein 60 Are Associated With the Presence and Severity of Coronary Artery Disease : Evidence for an Autoimmune Component of Atherogenesis Circulation, February 27, 2001; 103(8): 1071 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kramer, P. Harcos, Z. Prohaszka, L. Horvath, I. Karadi, M. Singh, A. Csaszar, L. Romics, and G. Fust Frequencies of Certain Complement Protein Alleles and Serum Levels of Anti-Heat-Shock Protein Antibodies in Cerebrovascular Diseases Stroke, November 1, 2000; 31(11): 2648 - 2652. [Abstract] [Full Text] [PDF]
|
|