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Distinguished effects of antiphospholipid antibodies and anti-oxidized LDL antibodies on oxidized LDL uptake by macrophages

Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

K. Tada

Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

H. Itabe

Department of Biological Chemistry, Showa University School of Pharmaceutical Sciences, Tokyo, Japan

T. Ueno

Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

P.-H. Liu

Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

A. Tsutsumi

Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan

M. Kuwana

Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

T. Yasuda

Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

Y. Shoenfeld

Department of Medicine B and Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Isreal, Incumbent of the Laura Schwarz-Kipp Chair for Research for Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

P.G. de Groot

Thrombosis and Haemostasis Laboratory, Department of Clinical Chemistry and Haematology, University Medical Center, Utrecht, The Netherlands

E. Matsuura

Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, eijimatu{at}md.okayama-u.ac.jp

Several interpretations have been made regarding the specificity of antiphospholipid antibodies and antibodies against oxidized low-density lipoprotein (oxLDL), but these are still controversial. In the present study, we delineated specificity of these two types of antibodies and analyzed their regulatory effect on oxLDL and/or β ²-glycoprotein I (β²GPI) binding to macrophages. Scavenger receptor-mediated binding of oxLDL (or its β²GPI complexes) to macrophages was observed and the binding was partly prevented by β ²GPI. The IgG monoclonal anti-β²GPI antibody (WB-CAL-1), which was derived from NZW x BXSB F1 mouse (a model of antiphospholipid syndrome), significantly increased the oxLDL/β²GPI binding to macrophages. In contrast, IgM anti-oxLDL natural antibody, EO6 (derived from apoe ^-/- mouse), prevented the binding. Different antigenic specificity of these antibodies to oxLDL and its β²GPI complexes was also confirmed in TLC—ligand blot and ELISA. Thus, IgG anti-β² GPI autoantibodies contribute to lipid metabolism (housekeeping of oxLDL by macrophages) whereas IgM natural anti-oxLDL antibodies may protect against atherogenesis. In addition, in vitro data suggest that relatively high dose of intravenous immunoglobulin preparations (mainly contain IgG anti-oxLDL antibodies) might also prevent atherogenesis by inhibiting the oxLDL binding to macrophages. Lupus (2007) 16, 929—938.

Key Words: anticardiolipin antibody • antiphospholipid syndrome • atherosclerosis • β2-glycoprotein I • oxidized low-density lipoprotein

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