title: Intracellular trafficking of beta2-glycoprotein I complexes with lipid vesicles in macrophages: implications on the development of antiphospholipid syndrome.
abstract: Beta(2)-glycoprotein I (beta(2)GPI) is known as a major autoantigen for antiphospholipid antibodies. Our recent data show that binding of beta(2)GPI to oxidized low-density lipoprotein (oxLDL) or to liposomes containing anionic phospholipid(s) may facilitate the presentation of beta(2)GPI's epitope by macrophages/dendritic cells to autoreactive T cells. In the present study, we investigated intracellular trafficking of beta(2)GPI and its complexes with oxLDL or liposomes containing phosphatidylserine (PS-liposomes) in mouse macrophage-like J774 cells. A relatively small amount of non-complexed beta(2)GPI was taken up and stagnated in the late endosome after incubating for 16h. In contrast, beta(2)GPI complexes with oxLDL or PS-liposomes were transported into the lysosome. In the presence of the IgG anti-beta(2)GPI autoantibody, WB-CAL-1, beta(2)GPI/oxLDL complexes were rapidly incorporated into intracellular space and were finally localized in the lysosome. Interestingly, in vitro pulses by beta(2)GPI/oxLDL complexes together with WB-CAL-1 led to the expression of membranous CD36 as well as Fcgamma type I receptors (FcgammaRI). These observations suggest that IgG immune complexes of beta(2)GPI/oxLDL provide not only FcgammaRI- but also scavenger receptor-mediated uptake of beta(2)GPI/oxLDL complexes by macrophages. Thus, beta(2)GPI/oxLDL complexes as a major atherogenic autoantigen and IgG anti-beta(2)GPI autoantibodies may facilitate antigen presentation and foam cell formation in antiphospholipid syndrome.
authors.affiliation: Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Kajiwara
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Yasuda
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
mesh_terms: D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology* / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002460:Cell Line; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism*; D008081:Liposomes / Q000276:immunology / Q000378:metabolism; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D051116:Receptors, Scavenger / Q000276:immunology / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*