RRC ID 43103
Author Kajiwara T, Yasuda T, Matsuura E.
Title Intracellular trafficking of beta2-glycoprotein I complexes with lipid vesicles in macrophages: implications on the development of antiphospholipid syndrome.
Journal J. Autoimmun.
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.
Volume 29(2-3)
Pages 164-73
Published 2007-9
DOI 10.1016/j.jaut.2007.07.003
PII S0896-8411(07)00082-0
PMID 17826950
MeSH Animals Antibodies, Antiphospholipid / immunology* Antibodies, Antiphospholipid / metabolism Antigen-Antibody Complex / metabolism Antiphospholipid Syndrome / immunology* Autoantibodies / immunology Autoantigens / immunology Cell Line Endosomes / immunology Endosomes / metabolism Lipoproteins, LDL / immunology Lipoproteins, LDL / metabolism* Liposomes / immunology Liposomes / metabolism Lysosomes / immunology Lysosomes / metabolism Macrophages / cytology Macrophages / immunology* Mice Receptors, Scavenger / immunology Receptors, Scavenger / metabolism beta 2-Glycoprotein I / immunology* beta 2-Glycoprotein I / isolation & purification beta 2-Glycoprotein I / metabolism*
IF 7.607
Times Cited 31
Human and Animal Cells