Involvement of β₂-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages

Anticardiolipin antibodies (aCL) in the sera of patients with antiphospholipid syndrome (APS) recognize an altered structure of β₂-glycoprotein I (β₂-GPI) interacting with solid-phase negatively charged phospholipids. β₂-GPI bound to Cu²⁺-oxidized plasma lipoproteins, i.e. oxidized very low-density lipoprotein (oxVLDL), oxidized low-density lipoprotein (oxLDL), or oxidized high-density lipoprotein (oxHDL). β₂-GPI inhibited in vitro uptake, i.e. cell surface binding, cellular association, and proteolytic degradation of oxLDL by murine macrophage J774A.1 cells. The binding of oxLDL to the macrophages was inhibited by the addition of polyinosinic acid (poly (I)), a competitor of the scavenger receptor, but not by another polyanionic acid, polycytidylic acid (poly (C)). Conversely, the binding of oxLDL was significantly increased by the simultaneous addition of human β₂-GPI and monoclonal aCL derived from NZW x BXSB F₁ (WB F₁) mice, an animal model of APS, or anti-β₂-GPI antibodies from BALB/c mice immunized with human β₂-GPI. These findings indicate that β₂-GPI may be an antiatherogenic protein and that the autoimmune response against β₂-GPI may have a role in the development of atherosclerosis in APS.