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

Toshimitsu Kajiwara, Tatsuji Yasuda, Eiji Matsuura

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)164-173
Number of pages10
JournalJournal of Autoimmunity
Volume29
Issue number2-3
DOIs
Publication statusPublished - Sep 2007

Keywords

  • Antiphospholipid antibodies
  • Antiphospholipid syndrome
  • Intracellular trafficking
  • Oxidized low-density lipoprotein
  • β-Glycoprotein I

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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