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.
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Journal |
J Autoimmun
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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 |
2007-1-1
|
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 |
6.658
|
Times Cited |
37
|
WOS Category
|
IMMUNOLOGY
|
Resource |
Human and Animal Cells |
|