期刊
INFLAMMATION RESEARCH
卷 62, 期 2, 页码 127-132出版社
SPRINGER BASEL AG
DOI: 10.1007/s00011-012-0579-7
关键词
Adhesion; Inflammation; Neutrophil; Statin; Rho GTPase
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
- CNPq, Brazil
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-alpha 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-alpha, and this increased expression was also inhibited by simvastatin. TNF-alpha 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-alpha-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据