Antiphospholipid antibodies, thrombin and LPS activate brain endothelial cells and Ras-dependent pathways through distinct mechanisms

Ramona Aronovich, David Gurwitz, Yoel Kloog, Joab Chapman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The antiphospholipid syndrome (APS) commonly affects the central nervous system through mechanisms that may include small vessel pathology and activation of thrombin. Antiphospholipid antibodies (aPL) activate endothelial cells but the specific activation of brain vascular endothelial cells (BVEC) and the receptors and signaling pathways involved have not been fully characterized. Objective: To examine whether aPL, the inflammatory stimulant lipopolysacharide (LPS) and thrombin activate BVECs through a Ras-dependent pathway. Methods: Rat BVEC (G8) were grown to confluence on 24-well plates. IgG was purified from 8 APS patients on a protein G column. Phosphorylation of ERK in the BVEC was measured by immunoblot utilizing a specific antibody. Results: Significant phosphorylation of ERK was measured following exposure of the cells to LPS and thrombin and this was blocked by the Ras inhibitor farnesylthiosalicylate (FTS). aPL IgG (1:100 relative to serum) from 7/8 patients also induced phosphorylation of ERK. Conclusions: Activation of the Ras-ERK pathway is an effect of both APS IgG and thrombin. This pathway is potentially amenable to drugs such as FTS and may serve as a therapeutic target in APS.

Original languageEnglish
Pages (from-to)781-788
Number of pages8
JournalImmunobiology
Volume210
Issue number10
DOIs
StatePublished - 13 Dec 2005

Keywords

  • Antiphospholipid syndrome
  • Brain
  • ERK
  • Endothelial cells
  • Thrombin

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