Published online before print October 6, 2005, doi: 10.1161/01.ATV.0000189298.62240.5d
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© 2005 American Heart Association, Inc.
Vascular Biology |
Upregulation of Proinflammatory Proteins Through NF-
B Pathway by Shed Membrane Microparticles Results in Vascular Hyporeactivity
From Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires (A.T., K.C., C.M., F.M., R.A.), UMR CNRS 7034, Illkirch, France; Dipartimento di Farmacologia e Fisiologia Umana (A.T., D.M.-C.), Università di Bari, Italia; Institut d’Hématologie et d’Immunologie (M.C.M., B.H., J.-M.F.), Université Louis Pasteur, Strasbourg, France & Unité 143 INSERM, Le Kremlin-Bicêtre, France
Correspondence to Dr Ramaroson Andriantsitohaina, UMR CNRS 7081, Faculté de Pharmacie, 74, route du Rhin, 67401 Illkirch, France. E-mail ramaroson.andriantsitohaina{at}pharma.u-strasbg.fr
Objective— Microparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation, including apoptosis. The present study was designed in dissecting the effects evoked by microparticles on vascular reactivity.
Methods and Results— Microparticles from either apoptotic T lymphocytic cells or from plasma of diabetic patients with vascular complications induced vascular hyporeactivity in response to vasoconstrictor agents in mouse aorta. Hyporeactivity was reversed by nitric oxide (NO) synthase plus cyclooxygenase-2 inhibitors, and associated with an increased production of vasodilatory products such as NO and prostacyclin. Microparticles induced an upregulation of proinflammatory protein expressions, inducible NO-synthase and cyclooxygenase-2, mainly in the medial layer of the vessels as evidenced by immunochemical staining. In addition, microparticles evoke NF-
B activation probably through the interaction with the Fas/Fas Ligand pathway. Finally, in vivo treatment of mice with lymphocyte-derived MPs induces vascular hyporeactivity, which was reversed by the combination of NO and cyclooxygenase-2 inhibitors.
Conclusion— These data provide a rationale to explain the paracrine role of microparticles as vectors of transcellular exchange of message in promoting vascular dysfunction during inflammatory diseases.
Microparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation. T cell–derived microparticles induce in vivo and in vitro vascular hyporeactivity associated with NO and prostacyclin production. Microparticles induce inducible NO synthase and cyclooxygenase-2, and evoke NF-B activation through Fas/FasLigand pathway. Microparticles promote vascular dysfunction during inflammatory diseases.
Key Words: Fas/Fas Ligand • microvesicles • proinflammatory proteins • vascular dysfunction • vasoactivity
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