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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #186820

Title: Anti-OxLDL IgG blocks OxLDL interaction with CD36, but promotes FcyR, CD32A-dependent inflammatory cell adhesion

Author
item NAGARAJAN, SHANMUGAM

Submitted to: Immunology Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/26/2006
Publication Date: 1/15/2007
Citation: Nagarajan, S. 2007. Anti-OxLDL IgG blocks OxLDL interaction with CD36, but promotes FcyR, CD32A-dependent inflammatory cell adhesion. Immunology Letters. 108(1):52-61.

Interpretive Summary: Heart attack one of the major causes of death in the United States. Thickening of blood vessels causes this disease. This process is called atherosclerosis. Coating blood vessels with bad cholesterol, or LDL, cause atherosclerosis. In our body, LDL undergoes chemical modification. One of the chemically modified LDL is known as oxidized-LDL. Formation of oxidized-LDL leads to generation of antibody response. This study examined whether antibody response contributes to the progression of the disease. Our study demonstrated that antibody generation results in attachment of blood cells to artery specific cells. We also show that blood cell sticking is caused by a group of proteins. Future studies will try to find if dietary intervention early in life could inhibit the generation of oxLDL and antibody response.

Technical Abstract: Generation of antibody against oxidized-low-density lipoprotein (oxLDL) during atherosclerosis could cause formation of oxLDL immune complexes (oxLDL-IC) on the vascular bed owing to oxLDL-deposited onto endothelial cells. In this report, we examined the role of Fcgamma receptors (Fc'R) in mediating monocyte adhesion to oxLDL-IC deposited on vascular endothelial cells. Human monocytic cell lines U937 and THP-1 adhered to oxLDL-IC and MDALDL-IC-coated plates, and antibody blocking studies showed that this adhesion is mediated by CD32A. As monocytes express CD36 and CD32A, receptors for oxLDL and oxLDL-IC, respectively, their relative contribution to this adhesion was assessed using CHOK1 cells expressing CD32A or CD32 and CD36. At all the concentrations of oxLDL-IC, anti-CD32 monoclonal antibody (mAb) completely inhibited CD32A-single transfectants adhesion. In the CD32A-CD36 double transfectants, anti-CD32 mAb inhibited about 20% of adhesion of cells at lower concentration of oxLDL-IC, however most of the adhesion (80%) is blocked at higher concentration of oxLDL-IC. An endothelial cell adhesion assay using oxLDL-IC-coated endothelial cells showed anti-CD36 mAb inhibited only about 15% of adhesion, while anti-CD32 mAb showed 85% inhibition of adhesion of CHOK1-CD32A or CD32A-CD36 double transfectants to MDALDL-IC and oxLDL-IC-deposited-endothelial cells, further confirming the findings from oxLDL-IC coated plate assays. Similar findings were observed with peripheral blood monocytes and platelets, suggesting the CD32A-mediated adhesion is not cell type specific. Further, PBMC adhesion to oxLDL-IC deposited endothelial cells resulted in secretion of pro-inflammatory chemokines, MCP-1, IL-8. Collectively, these findings suggest that CD32A plays a major role in mediating the adhesion of CD32A-CD36 positive cells such as monocytes to oxLDL-IC deposited endothelium. In conclusion, the findings from this study suggest that, when a strong antibody response occurs against ox-LDL, Fc'R could play a vital role in promoting monocyte adhesion and subsequent chemokine release. Thus, the Fc'R-mediated interaction between inflammatory and endothelial cells leading to vascular injury could contribute to the progression of atherosclerosis.