Anti-OxLDL IgG blocks OxLDL interaction with CD36, but promotes FcgammaR, CD32A-dependent inflammatory cell adhesion.
Generation of antibodies against oxidized-low-density lipoproteins (oxLDL) during atherosclerosis could result in the formation and deposition of oxLDL immune complexes (oxLDL-IC) on the vascular endothelial cells. Inflammatory cells express scavenger receptor (SR such as CD36) and Fcgamma receptor (FcgammaR: CD32A and CD64) that can bind to oxLDL and oxLDL-IC, respectively. Hence, depending on anti-oxLDL IgG titer, circulating monocytes could adhere to endothelium to oxLDL-IC-coated vascular bed via either FcgammaR and/or CD36. In this study, we determined the relative contribution of SR and FcgammaR in mediating monocyte interaction with oxLDL-IC deposited on vascular bed. At saturating levels of anti-oxLDL IgG concentration, monocytic cells adhered to oxLDL-IC and this adhesion is completely blocked by anti-CD32A mAb. Using CHOK1-CD32A-CD36 cells expressing equal levels of CD32A and CD36, it was observed that at lower concentrations of anti-oxLDL IgG, CD32A and CD36 contribute about 75% and 25% of cell adhesion, respectively, while at higher concentrations of anti-oxLDL IgG the adhesion is completely CD32A-dependent. CD32A-dependent adhesion was further confirmed with peripheral blood monocytes and platelets that express 2- to 5-fold higher levels of CD36 compared to CD32A. Further, PBMC adhesion to oxLDL-IC-deposited endothelial cells induced secretion of pro-inflammatory chemokines, MCP-1 and IL-8. Our results demonstrate that anti-oxLDL IgG blocks oxLDL interaction with SR such as CD36, whereas oxLDL-IC formation promotes monocyte adhesion and subsequent chemokine release through FcgammaR. These findings suggest a role for FcgammaR-mediated inflammatory cell activation in the progression of atherosclerosis.
Nagarajan
Shanmugam
S
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Arkansas Children's Nutrition Center, RM N2021C, 1120 Marshall Street, Little Rock, AR 72202, USA. NagarajanShanmugam@uams.edu
D000936:Antigen-Antibody Complex / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism* / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D017452:Receptors, IgG / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D018955:CD36 Antigens; D018925:Chemokines; C080568:Fc gamma receptor IIA; D007136:Immunoglobulins; D008077:Lipoproteins, LDL; D017452:Receptors, IgG; C099252:oxidized low density lipoprotein