The involvement of CD36 in monocyte activation by antiphospholipid antibodies

M. Kato, T. Atsumi, K. Oku, O. Amengual, H. Nakagawa, Y. Fujieda, K. Otomo, T. Horita, S. Yasuda, T. Koike

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7 Citations (Scopus)

Abstract

Background: CD36, known as a scavenger receptor, is a transmembrane glycoprotein expressed on monocytes, platelets and endothelial cells, recognizes multiple ligands, including phosphatidylserine, and regulates atherogenesis and thrombosis. The objective of this study is to investigate the possible involvement of CD36 in the pathophysiology of thrombosis in patients with antiphospholipid syndrome (APS). Methods: First, rs3765187, a missense mutation linked to CD36 deficiency, was investigated by TaqMan polymerase chain reaction (PCR) genotyping method in 819 Japanese, including 132 patients with APS, 265 with systemic lupus erythematosus (SLE) in the absence of APS, and 422 healthy subjects. Then, the involvement of CD36 in antiphospholipid antibody (aPL)-induced tissue factor (TF) expression was examined using CD36-null mice or anti-CD36. Purified IgG from patients with APS and a monoclonal phosphatidylserine-dependent antiprothrombin antibody were used in these experiments. TF expression was tested by real-time PCR and flow cytometry. Results: Minor allele carrier of rs3765187 was less frequent in patients with APS (3.8% p=0.032), but not in patients with SLE in the absence of APS (7.9% p=0.32), compared with healthy subjects (10.2%). The aPL-induced TF expression was significantly suppressed on peritoneal macrophages from CD36-null mice compared to wild type and significantly inhibited by anti- CD36 on human monocytes. Conclusions: The gene mutation linked to CD36 deficiency was less frequent in patients with APS. The deficient or suppressed CD36 function significantly reduced aPL-induced TF expression in vitro. Taken together, in a susceptible background CD36 scavenger receptor function may be involved in the thrombotic pathophysiology in patients with APS.

Original languageEnglish
Pages (from-to)761-771
Number of pages11
JournalLupus
Volume22
Issue number8
DOIs
Publication statusPublished - 2013 Jul 1
Externally publishedYes

Keywords

  • Antiphospholipid syndrome
  • lupus anticoagulant
  • scavenger receptor
  • thrombosis

ASJC Scopus subject areas

  • Rheumatology

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    Kato, M., Atsumi, T., Oku, K., Amengual, O., Nakagawa, H., Fujieda, Y., Otomo, K., Horita, T., Yasuda, S., & Koike, T. (2013). The involvement of CD36 in monocyte activation by antiphospholipid antibodies. Lupus, 22(8), 761-771. https://doi.org/10.1177/0961203313490242