| Autor: |
Mateo T; Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain., Naim Abu Nabah Y, Losada M, Estellés R, Company C, Bedrina B, Cerdá-Nicolás JM, Poole S, Jose PJ, Cortijo J, Morcillo EJ, Sanz MJ |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 2007 Sep 15; Vol. 110 (6), pp. 1895-902. Date of Electronic Publication: 2007 Jun 26. |
| DOI: |
10.1182/blood-2007-01-070607 |
| Abstrakt: |
Angiotensin II (Ang-II) exerts inflammatory activity and is involved in different cardiovascular disorders. This study has evaluated the involvement of tumor necrosis factor alpha (TNFalpha) in the leukocyte accumulation elicited by Ang-II. Ang-II (1 nM intraperitoneally in rats) induced TNFalpha release at 1 hour followed by neutrophil and mononuclear cell recruitment. The administration of an antirat TNFalpha antiserum had no effect on Ang-IIinduced neutrophil accumulation but inhibited the infiltration of mononuclear cells and reduced CC chemokine content in the peritoneal exudate. Pretreatment with either an anti-TNFalpha or an anti-IL-4 antiserum decreased Ang-II-induced arteriolar mononuclear leukocyte adhesion by 68% and 60%, respectively, in the rat mesenteric microcirculation. While no expression of TNFalpha was found in the postcapillary venules of Ang-II-injected animals, this cytokine was clearly up-regulated in the arterioles. Stimulation of human umbilical arterial endothelial cells (HUAECs) or isolated human mononuclear cells with 1 microM Ang-II caused increased TNFalpha mRNA expression and protein. Neutralization of TNFalpha activity reduced Ang-II-induced MCP-1, MCP-3, and RANTES release from HUAECs and MIP-1alpha from blood cells. In conclusion, the selective mononuclear leukocyte adhesion to Ang-II-stimulated arterioles is largely mediated by TNFalpha in cooperation with constitutive IL-4. Therefore, neutralization of TNFalpha activity may help to prevent mononuclear cell infiltration and the progression of the atherogenic process. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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