title: Angiotensin II-induced mononuclear leukocyte interactions with arteriolar and venular endothelium are mediated by the release of different CC chemokines.
abstract: Angiotensin II (Ang-II) is associated with atherogenesis and arterial subendothelial mononuclear leukocyte infiltration. We have demonstrated that Ang-II causes the initial attachment of mononuclear cells to the arteriolar endothelium. We now report on the contribution of CC chemokines to this response. Intraperitoneal administration of 1 nM Ang-II induced MCP-1, RANTES, and MIP-1alpha generation, maximal at 4 h, followed by mononuclear leukocyte recruitment at 8 and 24 h. Using intravital microscopy within the rat mesenteric microcirculation 4 h after exposure to 1 nM Ang-II, arteriolar mononuclear cell adhesion was 80-90% inhibited by pretreatment with Met-RANTES, a CCR1 and CCR5 antagonist, or an anti-MCP-1 antiserum, without affecting the increased endothelial expression of P-selectin and VCAM-1. Conversely, leukocyte interactions with the venular endothelium, although inhibited by Met-RANTES, were little affected by the anti-MCP-1. Using rat whole blood in vitro, Ang-II (100 nM) induced the expression of monocyte CD11b that was inhibited by Met-RANTES but not by anti-MCP-1. Stimulation of human endothelial cells (human umbilical arterial endothelial cells and HUVECs) with 1-1000 nM Ang-II, predominantly acting at its AT(1) receptor, induced the release of MCP-1 within 1 h, RANTES within 4 h, and MCP-3 within 24 h. Eotaxin-3, a natural CCR2 antagonist, was released within 1 h and may delay mononuclear cell responses to MCP-1. Therefore, Ang-II-induced mononuclear leukocyte recruitment at arterioles and venules is mediated by the production of different CC chemokines. Thus, Ang-II may be a key molecule in the initial attachment of mononuclear cells to the arterial endothelium in cardiovascular disease states where this event is a characteristic feature.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, Avenida Blasco Ibañez 15, E-46010 Valencia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Mateo
authors.forename: Yafa Naim
authors.initials: YN
authors.lastname: Abu Nabah
authors.forename: May
authors.initials: M
authors.lastname: Abu Taha
authors.forename: Manuel
authors.initials: M
authors.lastname: Mata
authors.forename: Miguel
authors.initials: M
authors.lastname: Cerdá-Nicolás
authors.forename: Amanda E I
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Issekutz
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Morcillo
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jose
authors.forename: Maria-Jesus
authors.initials: MJ
authors.lastname: Sanz
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D000075906:Chemokine CCL26; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology; D019742:Chemokines, CC / Q000096:biosynthesis / Q000378:metabolism*; D004727:Endothelium / Q000098:blood supply / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014470:Umbilical Cord / Q000187:drug effects / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C120429:CCL26 protein, human; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D000075906:Chemokine CCL26; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II