INVOLVEMENT OF BETA(2)-GLYCOPROTEIN-I AND ANTICARDIOLIPIN ANTIBODIES IN OXIDATIVELY MODIFIED LOW-DENSITY-LIPOPROTEIN UPTAKE BY MACROPHAGES

Anticardiolipin antibodies (aCL) in the sera of patients with antiphos pholipid syndrome (APS) recognize an altered structure of beta 2-glyco protein I (beta 2-GPI) interacting with solid-phase negatively charged phospholipids. beta(2)-GPI bound to Cu2+-oxidized plasma lipoproteins , i.e. oxidized very low-density lipoprotein (oxVLDL), oxidized low-de nsity lipoprotein (oxLDL), or oxidized high-density lipoprotein (oxHDL ). beta 2-GPI inhibited in vitro uptake, i.e. cell surface binding, ce llular association, and proteolytic degradation of oxLDL by murine mac rophage J774A.1 cells. The binding of oxLDL to the macrophages was inh ibited by the addition of polyinosinic acid (poly (I)), a competitor o f the scavenger receptor, but not by another polyanionic acid, polycyt idylic acid (poly (C)). Conversely, the binding of oxLDL was significa ntly increased by the simultaneous addition of human beta(2)-GPI and m onoclonal aCL derived from NZW x BXSB F-1 (WE F-1) mice, an animal mod el of APS, or anti-beta(2)-GPI antibodies from BALB/c mice immunized w ith human beta(2)-GPI. These findings indicate that beta(2)-GPI may be an antiatherogenic protein and that the autoimmune response against b eta(2)-GPI may have a role in the development of atherosclerosis in AP S.