title: Evidence of a role for both anti-Hsp70 antibody and endothelial surface membrane Hsp70 in atherosclerosis.
abstract: Although previous studies have shown that autoantigens such as Hsps have been implicated by induction of an autoimmune process in the development of atherosclerosis, the exact role of anti-Hsp70 antibody in atherosclerosis is unknown. In the present study, the levels of anti-Hsp70 autoantibodies and oxidized low density lipoprotein (OxLDL) were all significantly increased, and they were strongly correlated in an atherosclerosis model. After the endothelial cells were incubated with 20 μg/mL OxLDL for 12 h at 37 °C and followed by 90 min recovery, Hsp70 positive staining of OxLDL-treated endothelial cells was observed on the cell surface in immunostaining and flow cytometric analysis. This membrane Hsp70 was not from culture supernatant Hsp70 and binding of extracellular Hsp70 but was defined as endothelial surface membrane Hsp70. Furthermore, only in the OxLDL-treated group, but not in the untreated group, (51)Cr-labeled endothelial cells were lysed by anti-Hsp70 antibody (BD091, Ig(AS)) in the presence of either complement or peripheral blood mononuclear cells. Control antibodies, including Ig(Nor), mAb to Hsp70 (SPA-810), and mAbs to Factor VIII, α-actin, and CD3 showed no cytotoxic effects. In conclusion, anti-Hsp70 antibodies could be reacting with the endothelial surface membrane Hsp70 induced by OxLDL and were able to mediate endothelial cytotoxicity. There is a possibility that a humoral immune reaction to endothelial surface membrane Hsp70 may play an important role in the pathogenesis of atherosclerosis.
authors: Institute of Medical Equipment, Tianjin, People's Republic of China.
authors: Xue
authors: X
authors: Leng
authors: Xinxing
authors: X
authors: Wang
authors: Wei
authors: W
authors: Pang
authors: Rui
authors: R
authors: Zhan
authors: Zhiqing
authors: Z
authors: Zhang
authors: Liqun
authors: L
authors: Wang
authors: Xiujie
authors: X
authors: Gao
authors: Lingjia
authors: L
authors: Qian
mesh_terms: D000199:Actins / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005169:Factor VIII / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D017252:CD3 Complex; D018840:HSP70 Heat-Shock Proteins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D005169:Factor VIII