%0 Journal Article
%T Natural anti-oxLDL IgM monoclonal antibody in the pathogenesis of atherosclerosis<br>
%A Xuyang Feng
%A Ruifen Xu
%A Yan Gao
%A Haokao Gao
%A Zheng He
%A Haichang Wang
%A <br>
%J 老年心脏病学杂志(英文版)
%D 2009
%I Science Press
%X 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.
%K Atherosclerosis
%K macrophage
%K immunoglobulin M
%K Toll-like receptor 4
%K oxidized low-density lipoprotein<br>
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=A9DB1C13C87CE289EA38239A9433C9DC&cid=AD36F34DDC3BA7B0&jid=4DC702B3A2386A4814E2FF9CFB799B27&aid=B436C8ABD075A17D41916FE70C87FB48&yid=DE12191FBD62783C&vid=B31275AF3241DB2D&iid=CA4FD0336C81A37A&sid=ECE8E54D6034F642&eid=B6DA1AC076E37400&journal_id=1671-5411&journal_name=Journalofgeriatriccardiology:JGC&referenced_num=0&reference_num=36