title: Microparticles in multiple sclerosis and clinically isolated syndrome: effect on endothelial barrier function.
abstract: BACKGROUND
  Cell-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.
  
  
  RESULTS
  Platelet-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.
  
  
  CONCLUSIONS
  Plasma 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.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Marcos-Ramiro
authors.forename: Pedro
authors.initials: P
authors.lastname: Oliva Nacarino
authors.forename: Esther
authors.initials: E
authors.lastname: Serrano-Pertierra
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Blanco-Gelaz
authors.forename: Babette B
authors.initials: BB
authors.lastname: Weksler
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Romero
authors.forename: Pierre O
authors.initials: PO
authors.lastname: Couraud
authors.forename: Alberto
authors.initials: A
authors.lastname: Tuñón
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, C/ Nicolás Cabrera 1, Cantoblanco 28049, Madrid, Spain. jmillan@cbm.csic.es.
authors.forename: Jaime
authors.initials: J
authors.lastname: Millán
authors.forename: Eva
authors.initials: E
authors.lastname: Cernuda-Morollón
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D002199:Capillary Permeability; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002648:Child; D003711:Demyelinating Diseases / Q000503:physiopathology*; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000503:physiopathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000503:physiopathology*; D013917:Thrombin / Q000378:metabolism; D055815:Young Adult
chemical_list: D013917:Thrombin