C5a receptor-deficient mice are protected from thrombophilia and endothelial cell activation induced by some antiphospholipid antibodies

Zurina Romay-Penabad, Xiaowei Liu X, Guadalupe Montiel-Manzano, Elizabeth Papalardo De Martínez, Silvia S. Pierangeli

Research output: Chapter in Book/Report/Conference proceedingConference contribution

44 Scopus citations

Abstract

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 IgMNHS (3198 ± 2361 μm2 versus 585 ± 460 μm2). C5aR-/- mice treated with IgM-APS showed a significant reduction in thrombi size as compared with C5aR+/+ mice (676 ± 690 μm2 versus 3198 ± 2361 μm2; P = 0.001). IgG-APS enhanced thrombus formation significantly in C5aR+/+ when compared to IgG-NHS-treated mice (3507 ± 965 μm2 versus 1321 ± 798 μm 2), and these effects were not altered in C5aR-/- mice (3400 ± 1681 μm2). The data indicate that C5aR -/- mice are protected from the thrombogenic effects of some aPL antibodies.

Original languageEnglish (US)
Title of host publicationAutoimmunity, Part D
Subtitle of host publicationAutoimmune Disease, Annus Mirabilis
Pages554-566
Number of pages13
Volume1108
DOIs
StatePublished - Jun 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1108
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Antiphospholipid antibodies
  • Antiphospholipid syndrome
  • Complement activation
  • Endothelial cells
  • Thrombosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Romay-Penabad, Z., Liu X, X., Montiel-Manzano, G., De Martínez, E. P., & Pierangeli, S. S. (2007). C5a receptor-deficient mice are protected from thrombophilia and endothelial cell activation induced by some antiphospholipid antibodies. In Autoimmunity, Part D: Autoimmune Disease, Annus Mirabilis (Vol. 1108, pp. 554-566). (Annals of the New York Academy of Sciences; Vol. 1108). https://doi.org/10.1196/annals.1422.058