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C5a Receptor‐Deficient Mice Are Protected from Thrombophilia and Endothelial Cell Activation Induced by Some Antiphospholipid Antibodies
Author(s) -
ROMAYPENABAD ZURINA,
LIU X XIAOWEI,
MONTIELMANZANO GUADALUPE,
De MARTÍNEZ ELIZABETH PAPALARDO,
PIERANGELI SILVIA S.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1422.058
Subject(s) - thrombophilia , antiphospholipid syndrome , antibody , receptor , endothelial activation , immunology , chemistry , medicine , endothelium , thrombosis
: Recent findings indicate that complement activation—involving specifically C3 and C5—contributes to antiphospholipid (aPL)‐mediated thrombosis. Two complement effector pathways are initiated by the cleavage of C5, C5a and C5b, which leads to the formation of the C5b‐9 membrane attack complex. To delineate and distinguish the role of C5a from the C5b‐9 membrane attack complex seeded by C5b, we examined the in vivo effects (thrombosis) of aPL on C5a receptor‐deficient (C5aR −/− ) mice. C5aR −/− and C5aR +/+ mice were injected with IgM or with IgG from two different patients with APS (IgM‐APS or IgG‐APS) or with control IgM or IgG (IgM‐NHS or IgG‐NHS) twice. Complement fixing activity of the Ig fractions and anticardiolipin activity in the sera of the mice were determined by enzyme‐linked immunosorbent assay. Surgical procedures to study thrombus dynamics were performed. IgM‐APS but not IgG‐APS fixed C1q to cardiolipin‐coated plates. IgM‐APS significantly enhanced thrombus size in C5aR +/+ mice compared to C5aR +/+ mice treated with IgM‐NHS (3198 ± 2361 μm 2 versus 585 ± 460 μm 2 ). C5aR −/− mice treated with IgM‐APS showed a significant reduction in thrombi size as compared with C5aR +/+ mice (676 ± 690 μm 2 versus 3198 ± 2361 μm 2 ; P = 0.001). IgG‐APS enhanced thrombus formation significantly in C5aR +/+ when compared to IgG‐NHS‐treated mice (3507 ± 965 μm 2 versus 1321 ± 798 μm 2 ), and these effects were not altered in C5aR −/− mice (3400 ± 1681 μm 2 ). The data indicate that C5aR −/− mice are protected from the thrombogenic effects of some aPL antibodies.