Distinguished effects of antiphospholipid antibodies and anti-oxidized LDL antibodies on oxidized LDL uptake by macrophages.
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 beta( 2)-glycoprotein I (beta(2)GPI) binding to macrophages. Scavenger receptor-mediated binding of oxLDL (or its beta(2)GPI complexes) to macrophages was observed and the binding was partly prevented by beta( 2)GPI. The IgG monoclonal anti-beta(2)GPI antibody (WB-CAL-1), which was derived from NZW x BXSB F1 mouse (a model of antiphospholipid syndrome), significantly increased the oxLDL/beta(2)GPI 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 beta(2)GPI complexes was also confirmed in TLC-ligand blot and ELISA. Thus, IgG anti-beta(2) 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.
Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
K
K
Kobayashi
K
K
Tada
H
H
Itabe
T
T
Ueno
P-H
PH
Liu
A
A
Tsutsumi
M
M
Kuwana
T
T
Yasuda
Y
Y
Shoenfeld
P G
PG
de Groot
E
E
Matsuura
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000502:physiology*; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000502:physiology; D007075:Immunoglobulin M / Q000276:immunology / Q000502:physiology; D016756:Immunoglobulins, Intravenous / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D053482:beta 2-Glycoprotein I / Q000502:physiology*
D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein