Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression.
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.
Martin
Sophie
S
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Faculté de Pharmacie, Illkirch, France.
Tesse
Angela
A
Hugel
Bénédicte
B
Martínez
M Carmen
MC
Morel
Olivier
O
Freyssinet
Jean-Marie
JM
Andriantsitohaina
Ramaroson
R
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
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