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Urotensin II is a New Chemotactic Factor for UT Receptor-Expressing Monocytes¹

Jean-Pierre Segain^2,*,, Malvyne Rolli-Derkinderen^2,,, Nadine Gervois^,¶, Diane Raingeard de la Blétière^*,, Gervaise Loirand^,,|| and Pierre Pacaud^3,,

^* Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1280-Physiologie des Adaptations Nutritionnelles, Nantes, France; Faculté des Sciences, Université de Nantes, l’Institut du Thorax, Nantes, France; Institut National de la Santé et de la Recherche Médicale, Unité 533, Nantes, France; Institut National de la Santé et de la Recherche Médicale, Unité 601, Nantes, France; ^¶ Faculté de Médecine, Université de Nantes, Nantes, France; and ^|| Centre Hospitalier de l’Université Nantes, l’Institut du Thorax, Nantes, France

Urotensin II (U-II), a vasoactive cyclic neuropeptide which activates the G protein-coupled receptor UT receptor, exerts various cardiovascular effects and may play a role in the pathophysiology of atherosclerosis. In this study, we report that the UT receptor is expressed and functional on human PBMC and rat splenocytes. PBMC surface expression of the UT receptor was mainly found in monocytes and NK cells, also in a minority of B cells, but not in T cells. Stimulation of monocytes with LPS increased UT receptor mRNA and protein expression. Cloning and functional characterization of the human UT receptor gene promoter revealed the presence of NF-B-binding sites involved in the stimulation of UT receptor gene expression by LPS. Activation of the UT receptor by U-II induced chemotaxis with maximal activity at 10 and 100 nM. This U-II effect was restricted to monocytes. Analysis of the signaling pathway involved indicated that U-II-mediated chemotaxis was related to RhoA and Rho kinase activation and actin cytoskeleton reorganization. The present results thus identify U-II as a chemoattractant for UT receptor-expressing monocytes and indicate a pivotal role of the RhoA-Rho kinase signaling cascade in the chemotaxis induced by U-II.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Institut National de la Recherche Agronomique, Institut National de la Santé et de la Recherche Médicale, and the Région Pays de la Loire. M.R.-D. was supported by Centre National de la Recherche Scientifique.

² J.-P.S. and M.R.-D. contributed equally to this work.

³ Address correspondence and reprint requests to Prof. Pierre Pacaud, Institut National de la Santé et de la Recherche Médicale Unité 533 l’Institut du Thorax, Université de Nantes, Faculté des Sciences, 2 rue de la Houssinière, F-44322 Nantes, France. E-mail address: pierre.pacaud{at}univ-nantes.fr

⁴ Abbreviations used in this paper: DC, dendritic cell; U-II, urotensin-II; MLC, myosin L chain; PMN, polymorphonuclear cell; DC, dendritic cell; iDC, immature DC; mDC, mature DC; h, human; r, rat; Ct, cycle threshold; WT, wild type; MFI, mean fluorescence intensity; CAPE, caffeic acid phenethyl ester.