老年心脏病学杂志（英文版）2009，Vol.6Issue(1)：42-48,7.
Natural anti-oxLDL IgM monoclonal antibody in the pathogenesis of atherosclerosis
Natural anti-oxLDL IgM monoclonal antibody in the pathogenesis of atherosclerosis
Xuyang Feng 1Ruifen Xu 2Yan Gao 3Haokao Gao 4Zheng He 1Haichang Wang2
作者信息
- 1. Department of Cardiology, Xijing Hospital
- 2. Xi'an 710032, China
- 3. Department of Anesthesiology, Stomatology Hospital, the Fourth Military Medical University, Xi'an 710000, P.R.China
- 4. Department of Cardiology, PLA No. 323 Hospital, Xi'an 710054, P.R.China
- 折叠
摘要
Abstract
Objective To explore the role and the possible molecular mechanisms of natural anti-oxLDL IgM monoclonal antibody played and involved in pathogenesis of atherosclerosis. Methods Natural anti-oxLDL IgM monoclonal antibody 3A6 was generated by using standard hybridoma production techniques. Influence of 3A6 on formation of foam cells was observed by Oil Red O staining and affinity of Na125I-conjugated oxLDL on the naive and LPS-activated macrophages. After LPS stimulation on macrophages, anti-TLR4 neutralizing mAb, p38MAPK specific inhibitor SB203580, NF-kB specific inhibitor PDTC or RNAi targeting Fcα/μ receptor (Fcamr) were applied, respectively. Results Natural anti-oxLDL IgM monoclonal antibody 3 A6 were found specifically inhibit the binding of CuoxLDL to naive macrophages but not the binding of CuoxLDL to LPS-activated macrophages. It also promoted the formation of CuoxLDL-mediated foam macrophages. 3A6 F(ab')2 or pre-incubation with un-related IgM inhibited the binding of 3A6/CuoxLDL complex to LPS-activated macrophages. LPS up-regulated the expression of Fcamr in macrophages in a dose- and time-dependent manner, which was attenuated by treatment with anti-TLR4. LPS induced the phosphorylation of p38MAPK and translocation of NF-kB p65, contributing to the up-regulated expression of Fcα/μ receptor in macrophages. Conclusions Natural anti-oxLDL IgM monoclonal antibody 3A6 specifically inhibited the binding of CuoxLDL to naive macrophages in vitro. However, LPS, through the Toll-like receptor (TLR)4 receptor, activated the p38MAPK and NF-kB pathways and up-regulated the expression of Fcα/μ receptor in macrophages, which promoted the binding of 3A6/CuoxLDL complex to macrophages through binding with Fc fragments and the formation of foam macrophages. Therefore, our findings provide a new explanation why bacterial infection deteriorates the pathogenesis of atherosclerosis.关键词
Atherosclerosis/macrophage/immunoglobulin M/Toll-like receptor 4/oxidized low-density lipoprotein/Fcα/μ receptorKey words
Atherosclerosis/macrophage/immunoglobulin M/Toll-like receptor 4/oxidized low-density lipoprotein/Fcα/μ receptor分类
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Xuyang Feng,Ruifen Xu,Yan Gao,Haokao Gao,Zheng He,Haichang Wang..Natural anti-oxLDL IgM monoclonal antibody in the pathogenesis of atherosclerosis[J].老年心脏病学杂志（英文版）,2009,6(1):42-48,7.
