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Type: Artigo de periódico
Title: Simvastatin Abrogates Inflamed Neutrophil Adhesive Properties, In Association With The Inhibition Of Mac-1 Integrin Expression And Modulation Of Rho Kinase Activity.
Author: Silveira, Angélica Aparecida Antoniellis
Dominical, Venina Marcela
Lazarini, Mariana
Costa, Fernando Ferreira
Conran, Nicola
Abstract: Leukocytes play a primary role in vascular inflammation, and thus an understanding of the pathways involved in the activation of these cells and means to inhibit their consequent adhesion to the vessel wall is of significant interest. This study aimed to determine whether statins have a direct effect upon neutrophil adhesive properties under inflammatory conditions. Neutrophils from healthy individuals were subjected to adhesion assays (with fibronectin as ligand) and flow cytometry. In the presence of a TNF-α inflammatory stimulus, neutrophils displayed a rapid and substantial enhancement in their adhesive properties that was abrogated by preincubation of cells with simvastatin. Neutrophil surface expression of the Mac-1 integrin subunit, CD11b, was augmented by TNF-α, and this increased expression was also inhibited by simvastatin. TNF-α also induced neutrophil LFA-1 and Mac-1 activation, but this activation was not blocked by simvastatin. Interestingly, while addition of the isoprenoids, geranygerayl pyrophosphate and farnesyl pyrophosphate, to cells did not alter the effect of simvastatin on TNF-α-stimulated adhesion, concurrent incubation of cells with the Rho kinase (ROCK) inhibitor reversed the effects of simvastatin on neutrophil adhesion and CD11b expression. Simvastatin appears to have direct anti-inflammatory effects in neutrophils that may be mediated by modulation of ROCK activity.
Subject: Adolescent
Cell Adhesion
Cell Adhesion Molecules
Cells, Cultured
Hydroxymethylglutaryl-coa Reductase Inhibitors
Macrophage-1 Antigen
Middle Aged
Tumor Necrosis Factor-alpha
Young Adult
Citation: Inflammation Research : Official Journal Of The European Histamine Research Society ... [et Al.]. v. 62, n. 2, p. 127-32, 2013-Feb.
Rights: fechado
Identifier DOI: 10.1007/s00011-012-0579-7
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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