Intracellular trafficking of β₂-glycoprotein I complexes with lipid vesicles in macrophages: Implications on the development of antiphospholipid syndrome

β₂-Glycoprotein I (β₂GPI) is known as a major autoantigen for antiphospholipid antibodies. Our recent data show that binding of β₂GPI to oxidized low-density lipoprotein (oxLDL) or to liposomes containing anionic phospholipid(s) may facilitate the presentation of β₂GPI's epitope by macrophages/dendritic cells to autoreactive T cells. In the present study, we investigated intracellular trafficking of β₂GPI and its complexes with oxLDL or liposomes containing phosphatidylserine (PS-liposomes) in mouse macrophage-like J774 cells. A relatively small amount of non-complexed β₂GPI was taken up and stagnated in the late endosome after incubating for 16 h. In contrast, β₂GPI complexes with oxLDL or PS-liposomes were transported into the lysosome. In the presence of the IgG anti-β₂GPI autoantibody, WB-CAL-1, β₂GPI/oxLDL complexes were rapidly incorporated into intracellular space and were finally localized in the lysosome. Interestingly, in vitro pulses by β₂GPI/oxLDL complexes together with WB-CAL-1 led to the expression of membranous CD36 as well as Fcγ type I receptors (FcγRI). These observations suggest that IgG immune complexes of β₂GPI/oxLDL provide not only FcγRI- but also scavenger receptor-mediated uptake of β₂GPI/oxLDL complexes by macrophages. Thus, β₂GPI/oxLDL complexes as a major atherogenic autoantigen and IgG anti-β₂GPI autoantibodies may facilitate antigen presentation and foam cell formation in antiphospholipid syndrome.