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BMC Neuroscience

, 15:110

Neurobiology of disease

Abstract

BackgroundCell-derived microparticles are secreted in response to cell damage or dysfunction. Endothelial and platelet dysfunction are thought to contribute to the development of multiple sclerosis MS. Our aim here is, first, to compare the presence of microparticles of endothelial and platelet origin in plasma from patients with different clinical forms of MS and with clinically isolated syndrome. Second, to investigate the effect of microparticles on endothelial barrier function.

ResultsPlatelet-poor plasma from 95 patients 12 with clinically isolated syndrome, 51 relapsing-remitting, 23 secondary progressive, 9 primary progressive and 49 healthy controls were analyzed for the presence of platelet-derived and endothelium-derived microparticles by flow cytometry. The plasma concentration of platelet-derived and endothelium-derived microparticles increased in all clinical forms of MS and in clinically isolated syndrome versus controls. The response of endothelial barriers to purified microparticles was measured by electric cell-substrate impedance sensing. Microparticles from relapsing-remitting MS patients induced, at equivalent concentrations, a stronger disruption of endothelial barriers than those from healthy donors or from patients with clinically isolated syndrome. MS microparticles acted synergistically with the inflammatory mediator thrombin to disrupt the endothelial barrier function.

ConclusionsPlasma microparticles should be considered not only as markers of early stages of MS, but also as pathological factors with the potential to increase endothelial permeability and leukocyte infiltration.

KeywordsMultiple sclerosis Clinically isolated syndrome Microparticles Endothelial barrier function Thrombin AbbreviationsMSMultiple sclerosis

RRMSRelapsing, remitting MS

SPMSSecondary progressive MS

PPMSPrimary progressive MS

CISClinically isolated syndrome

CNSCentral nervous system

BBBBlood–brain barrier

PPPPlatelet-poor plasma

MPsMicroparticles

PMPsPlatelet-derived MPs

EMPsEndothelial-derived microparticles

ECEndothelial cell

HUVECHuman umbilical vein endothelial cell

TNFTumor necrosis factor

TEERTransendothelial electric resistance

ECISElectric cell-substrate impedance sensing

AnxVAnnexin V

SDStandard deviation.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-15-110 contains supplementary material, which is available to authorized users.

Beatriz Marcos-Ramiro, Pedro Oliva Nacarino contributed equally to this work.

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Autor: Beatriz Marcos-Ramiro - Pedro Oliva Nacarino - Esther Serrano-Pertierra - Miguel Ángel Blanco-Gelaz - Babette B Weksler -

Fuente: https://link.springer.com/







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