title: Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression.
abstract: BACKGROUND
  Microparticles (MPs) are membrane vesicles with procoagulant and proinflammatory properties released during cell activation. The present study was designed to dissect the effects evoked by T lymphocyte-derived MPs on vascular function.
  
  
  RESULTS
  MPs were produced by treatment of the human lymphoid CEM T cell line with actinomycin D or phytohemagglutinin. Incubation of mouse aortic rings with 30 nmol/L MPs resulted in a time-dependent impairment of acetylcholine-induced relaxation of precontracted vessels, with a maximal reduction after 24 hours. MPs also impaired shear stress-induced dilatation of mouse small mesenteric arteries by affecting the nitric oxide (NO) and prostacyclin but not the endothelium-derived hyperpolarizing factor components of the response. However, neither alteration of calcium signaling in response to agonists nor reduction of cyclooxygenase-1 expression accounted for the impairment of the NO and prostacyclin components of the endothelial response. The effect of MPs was rather because of a decrease in expression of endothelial NO synthase and an overexpression of caveolin-1. Furthermore, lymphocyte-derived MPs from diabetic patients or in vivo circulating MPs from either diabetic or HIV-infected patients reduced endothelial NO synthase expression. Finally, the effects of MPs on endothelial cells were not driven through CD11a/CD18 adhesion molecules or the Fas/FasL pathway.
  
  
  CONCLUSIONS
  MPs from T cells induce endothelial dysfunction in both conductance and resistance arteries by alteration of NO and prostacyclin pathways. MPs regulate protein expression for endothelial NO synthase and caveolin-1. These data contribute to a better understanding of the deleterious effects of enhanced circulating MPs observed in disorders with cardiovascular or immune complications.
authors.affiliation: Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Faculté de Pharmacie, Illkirch, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Martin
authors.forename: Angela
authors.initials: A
authors.lastname: Tesse
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Hugel
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Martínez
authors.forename: Olivier
authors.initials: O
authors.lastname: Morel
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Freyssinet
authors.forename: Ramaroson
authors.initials: R
authors.lastname: Andriantsitohaina
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001685:Biological Factors / Q000502:physiology; D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000276:immunology; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008563:Membrane Lipids / Q000737:chemistry; D008638:Mesenteric Arteries / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D010718:Phosphatidylserines / Q000737:chemistry; D010835:Phytohemagglutinins / Q000494:pharmacology; D044062:Prostaglandins I / Q000502:physiology; D013314:Stress, Mechanical; D013601:T-Lymphocytes / Q000187:drug effects / Q000648:ultrastructure*; D014664:Vasodilation / Q000502:physiology
chemical_list: D001685:Biological Factors; C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D008563:Membrane Lipids; D010718:Phosphatidylserines; D010835:Phytohemagglutinins; D044062:Prostaglandins I; C067410:endothelium-dependent hyperpolarization factor; D003609:Dactinomycin; D019335:Nitroarginine; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000109:Acetylcholine