Toll-like receptor 4 and β2 glycoprotein i interaction on endothelial cells

M. O. Borghi, E. Raschi, C. Grossi, C. B. Chighizola, P. L. Meroni

Research output: Contribution to journalArticlepeer-review

Abstract

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic events and/or pregnancy morbidity in the persistent presence of antiphospholipid antibodies (aPL). aPL targeting β2 glycoprotein I (anti-β2GPI Abs) provide the main pathogenic autoantibody subset. In monocytes, platelets and endothelial cells (ECs), the interaction of circulating aPL with membrane-bound β2GPI results in cell activation, and EC perturbation provides an important player in clotting. Several receptors have been suggested to mediate β2GPI/EC binding. AnnexinA2 provides a high-affinity binding site for β2GPI but, since it does not span the cell membrane, an adaptor protein is required to trigger signal. Consistent evidence supports the role of Toll-like receptor (TLR) 4 as co-receptor for β2GPI on ECs. β2GPI was recently reported to behave as lipopolysaccharide (LPS) scavenger. In monocytes, TLR4 activation was shown to be apparent, due to LPS/β2GPI complexes. Conversely, our findings in ECs demonstrate that β2GPI interacts directly with TLR4, and that such interaction may contribute to β2GPI-dependent aPL-mediated EC activation. LPS enhanced anti-β2GPI Ab binding to EC only at cell-activating concentrations, able to up-regulate TLR4. This in vitro model may explain why LPS behaves as a second hit increasing the expression of β2GPI in vascular tissues and triggering aPL-mediated thrombosis in vivo.

Original languageEnglish
Pages (from-to)1302-1304
Number of pages3
JournalLupus
Volume23
Issue number12
DOIs
Publication statusPublished - Oct 8 2014

Keywords

  • Anticardiolipin antibodies
  • antiphospholipid syndrome
  • thrombosis

ASJC Scopus subject areas

  • Rheumatology
  • Medicine(all)

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