Prevention of neutrophil extravasation by α2-adrenoceptor-mediated endothelial stabilization.

Autor:	Herrera-García AM; Departamento de Medicina, Facultad de Medicina, Universidad de La Laguna, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;, Domínguez-Luis MJ; Centro para la Investigación Biomédica de las Islas Canarias, Instituto de Tecnologías Biomedicas, Universidad de La Laguna, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;, Arce-Franco M; Servicio de Reumatología, Hospital Universitario de Canarias, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;, Armas-González E; Departamento de Medicina, Facultad de Medicina, Universidad de La Laguna, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;, Álvarez de La Rosa D; Departamento de Fisiología, Facultad de Medicina, Universidad de La Laguna, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;, Machado JD; Departamento de Farmacología, Facultad de Medicina, Universidad de La Laguna, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;, Pec MK; Departamento de Medicina, Facultad de Medicina, Universidad de La Laguna, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;, Feria M; Departamento de Farmacología, Facultad de Medicina, Universidad de La Laguna, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;, Barreiro O; Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Consejo Superior de Investigaciones Cientificas, 28029 Madrid, Spain; and., Sánchez-Madrid F; Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Consejo Superior de Investigaciones Cientificas, 28029 Madrid, Spain; and Servicio de Inmunología, Hospital Universitario de La Princesa, 28006 Madrid, Spain., Díaz-González F; Departamento de Medicina, Facultad de Medicina, Universidad de La Laguna, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain; Servicio de Reumatología, Hospital Universitario de Canarias, La Cuesta, 38320 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain; federico.diaz.gonzalez@gmail.com.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Sep 15; Vol. 193 (6), pp. 3023-35. Date of Electronic Publication: 2014 Aug 11.
DOI:	10.4049/jimmunol.1400255
Abstrakt:	Adrenergic receptors are expressed on the surface of inflammation-mediating cells, but their potential role in the regulation of the inflammatory response is still poorly understood. The objectives of this work were to study the effects of α2-adrenergic agonists on the inflammatory response in vivo and to determine their mechanism of action. In two mouse models of inflammation, zymosan air pouch and thioglycolate-induced peritonitis models, the i.m. treatment with xylazine or UK14304, two α2-adrenergic agonists, reduced neutrophil migration by 60%. The α2-adrenergic antagonist RX821002 abrogated this effect. In flow cytometry experiments, the basal surface expression of L-selectin and CD11b was modified neither in murine nor in human neutrophils upon α2-agonist treatment. Similar experiments in HUVEC showed that UK14304 prevented the activation-dependent upregulation of ICAM-1. In contrast, UK14304 augmented electrical resistance and reduced macromolecular transport through a confluent HUVEC monolayer. In flow chamber experiments, under postcapillary venule-like flow conditions, the pretreatment of HUVECs, but not neutrophils, with α2-agonists decreased transendothelial migration, without affecting neutrophil rolling. Interestingly, α2-agonists prevented the TNF-α-mediated decrease in expression of the adherens junctional molecules, VE-cadherin, β-catenin, and plakoglobin, and reduced the ICAM-1-mediated phosphorylation of VE-cadherin by immunofluorescence and confocal analysis and Western blot analysis, respectively. These findings indicate that α2-adrenoceptors trigger signals that protect the integrity of endothelial adherens junctions during the inflammatory response, thus pointing at the vascular endothelium as a therapeutic target for the management of inflammatory processes in humans. (Copyright © 2014 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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