title: Elevated endothelial microparticle-monocyte complexes induced by multiple sclerosis plasma and the inhibitory effects of interferon-beta 1b on release of endothelial microparticles, formation and transendothelial migration of monocyte-endothelial microparticle complexes.
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-beta 1b on release of EMP and on TEMIG of monocytes (mono) and monocytes:EMP complexes (mono:EMP) through the BMVEC. The effect of IFN-beta 1b on the release of EMP and the TEMIG of mono and mono:EMP was assessed by preincubating BMVEC cultures of IFN-beta 1b 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-beta 1b 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-beta 1b inhibited TEMIG and release of EMP, suggesting a role of EMP and a novel therapeutic mechanism for IFN-beta 1b in MS.
authors.affiliation: Wallace H Coulter Platelet Laboratory, Division of Hematology/Oncology, University of Miami School of Medicine, Miami, FL 33136, USA.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Jimenez
authors.forename: Wenche
authors.initials: W
authors.lastname: Jy
authors.forename: Lucia M
authors.initials: LM
authors.lastname: Mauro
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Horstman
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Ahn
authors.forename: Yeon S
authors.initials: YS
authors.lastname: Ahn
authors.forename: Alireza
authors.initials: A
authors.lastname: Minagar
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D001812:Blood-Brain Barrier / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009103:Multiple Sclerosis / Q000097:blood* / Q000276:immunology / Q000473:pathology; D010316:Particle Size; D020298:U937 Cells
chemical_list: D000276:Adjuvants, Immunologic; D000068576:Interferon beta-1b; D016899:Interferon-beta