Heat shock protein 60/65, beta 2-glycoprotein I and oxidized LDL as players in murine atherosclerosis.
We have made consecutive studies to prove that autoimmune factors can influence the progression of atherosclerosis in inbred and transgenic mice. C57BL/6 as well as LDL-receptor deficient mice were immunized with heat shock protein 65. LDL-RD and apolipoprotein E knockout (apoE KO) mice were immunized with human B-glycoprotein I. ApoE KO mice were immunized with oxidized LDL. In all immunized mice, a sustained humoral response to the provided antigen was elicited evident by high titers of antibodies by ELISA. A primary cellular immune response was also shown by thymidine incorporation studies employing the antigens in vitro. Immunization with hsp-65 and with beta 2-GPI served to enhance the progression atherosclerosis and led to an increase in the infiltration of CD3 in the subendothelial regions of the early plaques. Transfer of hsp-65 and beta 2-GPI reactive lymphocytes to syngenic mice led to enhancement of fatty streak formation. However, immunization with homologous oxLDL in apoE KO mice led to attenuation of lesion progression concomitant with the production of anti-oxLDL antibodies. Thus, autoimmune factors appear to influence early artherosclerosis progression in mice. If proven in humans these antigen specific responses may be harnessed for selective immunomodulation of the atherosclerotic plaque.
Shoenfeld
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Y
Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel. shoenfel@post.tau.ac.il
Harats
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D
George
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J
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001161:Arteriosclerosis / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology*; D018833:Chaperonins / Q000276:immunology*; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D053482:beta 2-Glycoprotein I
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C074119:heat-shock protein 65, Mycobacterium; C099252:oxidized low density lipoprotein; D018833:Chaperonins