Anti-Fcamr monoclonal antibody, clone UY72

Antibody exerts various immune responses via binding to Fc receptors expressed on immune cells. Although several reports have demonstrated that IgM prevents autoantibody production, the role of IgM Fc receptors is largely unknown. To analyze the involvement of Fc alpha/mu R (CD351), an Fc receptor for IgM and IgA expressed on B cells and follicular dendritic cells (FDCs), in IgM-mediated suppression of autoantibody production, we generated mice deficient in Fc alpha/mu R on the background of MRL/MpJ-Fas(lpr/lpr) (Fcamr(-vertical bar-)Fas(lpr/lpr) mice. Fcamr(-vertical bar-)Fas(lpr/lpr) mice showed significantly lower titers of IgG autoantibodies against double strand (ds) DNA, histone and cardiolipin in the sera than did Fcamr+/+Fas(lpr/lpr) mice. Moreover, Fcamr(-vertical bar-)Fas(lpr/lpr) mice showed higher survival rate at the ages of 28, 32 and 40 weeks old, compared with Fcamr(+/+)Fas(lpr/lpr) mice. These results suggest that Fc alpha/mu R enhances, rather than suppresses, autoantibody production. (C) 2013 Elsevier Ltd. All rights reserved.

Natural IgM antibodies against oxidized low-density lipoprotein (oxLDL) can inhibit the binding of oxLDL to macrophages and bacterial infection may deteriorate the pathogenesis of atherosclerosis. However, little is known about the molecular mechanisms underlying the action of bacterial lipopolysaccharide (LPS) in the binding of oxLDL to macrophages, contributing to the formation of foam macrophages. In this study, human monocytes-derived macrophages were cultured and incubated with purified human anti-oxLDL IgM antibodies (HAO-IgM), lipopolysaccharide (LPS) and oxLDL. The HAO-IgM were found specifically inhibited the binding of CuoxLDL to naive macrophages but failed to inhibit the binding of CuoxLDL to LPS-activated macrophages and promoted the formation of CuoxLDL-mediated foam macrophages. Furthermore, the HAO-IgM F(ab')(2) or pre-incubation with unrelated IgM inhibited the binding of HAOIgM/CuoxLDL complex to LPS-activated macrophages, suggesting that Fc alpha/mu receptor (Fcamr) may be responsible for the binding of HAO-IgM/CuoxLDL complex to LPS-activated macrophages. Indeed, LPS up-regulated the expression of Fcamr in macrophages in a dose-and time-dependent manner, which was diminished by treatment with anti-TLR4. In addition, LPS induced the phosphorylation of p38MAPK and translocation of NF-kappa B p65, contributing to the up-regulated expression of Fcamr in macrophages as treatment with specific inhibitor for p38MAPK (SB203580) or NF-kappa B (PDTC) attenuated the up-regulation of Fc alpha/mu receptor expression induced by LPS in macrophages. Inhibition of p38 MAPK and NF-kappa B-decreased the foam cells formation increased by Fcamr expression. These data demonstrated that LPS, through the TLR4 receptor, activated the p38MAPK and NF-kappa B pathways and up-regulate the expression of Fcamr in human macrophages, which promotes the binding of IgM/CuoxLDL complex to macrophages and the formation of foam cells. Therefore, our findings provide a new explanation why bacterial infection deteriorates the pathogenesis of atherosclerosis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.