Elevated endothelial microparticle-monocyte complexes induced by multiple sclerosis plasma and the inhibitory effects of interferon-β1b on release of endothelial microparticles, formation and transendothelial migration of monocyte-endothelial microparticle complexes

Joaquin J. Jimenez, Wenche Jy, Lucia M. Mauro, Lawrence L. Horstman, Eugene R Ahn, Yeon S. Ahn, Alireza Minagar

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Monocyte migration through the disrupted cerebral endothelial cell (EC) junctions plays an essential role in formation of multiple sclerosis (MS) demyelinating lesions. During pathogenesis of MS, activated ECs release endothelial microparticles (EMP), which possibly facilitate transendothelial migration (TEMIG) of monocytes. To assess functional roles of EMP in MS, specifically, their (i) interaction with monocytes, (ii) effect on monocyte TEMIG in an in vitro model of the brain microvascular endothelial cells (BMVEC), (iii) phenotypic profiles of EMP elicited by MS plasma and (iv) the effects of IFN-β1b on release of EMP and on TEMIG of monocytes (mono) and monocytes:EMP complexes (mono:EMP) through the BMVEC. The effect of IFN-β1b on the release of EMP and the TEMIG of mono and mono:EMP was assessed by preincubating BMVEC cultures of IFN-β1b prior to addition of plasma. Three EMP phenotypes, CD54, CD62E and CD31 were assayed. Plasma specimens from 20 patients with relapsing-remitting MS (11 in exacerbation, MS-E, and 9 in remission, ME-R) and 10 healthy controls were studied. Incubation of BMVEC with MS-E plasma yielded elevated levels of EMPCD54, EMP62E and EMPCD31 relative to MS-R and control plasmas. MS-E but not MS-R or control plasma also augmented TEMIG of monocytes, respectively. Mono:EMP complexes further augmented TEMIG relative to mono alone, but only in the presence of MS-E plasma; there was no significant effect with MS-R or control plasmas. The presence of IFN-β1b inhibited TEMIG of mono and mono:EMP by 20% and 30%, respectively. MS-E but not MS-R plasma elicited release of activation-derived EMP and enhanced TEMIG of mono and mono:EMP IFN-β1b inhibited TEMIG and release of EMP, suggesting a role of EMP and a novel therapeutic mechanism for IFN-β1b in MS.

Original languageEnglish (US)
Pages (from-to)310-315
Number of pages6
JournalMultiple Sclerosis
Volume11
Issue number3
DOIs
StatePublished - Jun 1 2005

Keywords

  • Endothelial microparticle
  • Exacerbation
  • Interferon-β1b
  • Monocyte
  • Multiple sclerosis
  • Remission

ASJC Scopus subject areas

  • Clinical Neurology

Fingerprint Dive into the research topics of 'Elevated endothelial microparticle-monocyte complexes induced by multiple sclerosis plasma and the inhibitory effects of interferon-β1b on release of endothelial microparticles, formation and transendothelial migration of monocyte-endothelial microparticle complexes'. Together they form a unique fingerprint.

  • Cite this