Urotensin II is a new chemotactic factor for UT receptor-expressing monocytes.
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-kappaB-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.
Segain
Jean-Pierre
JP
Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1280-Physiologie des Adaptations Nutritionnelles, Nantes, France.
Rolli-Derkinderen
Malvyne
M
Gervois
Nadine
N
Raingeard de la Blétière
Diane
D
Loirand
Gervaise
G
Pacaud
Pierre
P
D000199:Actins / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003001:Cloning, Molecular; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection; D014579:Urotensins / Q000276:immunology* / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis
D000199:Actins; D016328:NF-kappa B; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C029677:urotensin II; D020929:Mitogen-Activated Protein Kinase Kinases; D020742:rhoA GTP-Binding Protein