Bioactivity of nitrolinoleate: effects on adhesion molecules and CD40-CD40L system
Bioactivity of nitrolinoleate: effects on adhesion molecules and CD40-CD40L system
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DOI：
10.1016/j.jnutbio.2008.12.004
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发表时间：
2010-02-01
影响因子：
5.6
通讯作者：
Parra Abdalla, Dulcineia Saes
中科院分区：
文献类型：
--
作者：
Faine, Luciane A.;Cavalcanti, Danielle M. H.;Parra Abdalla, Dulcineia Saes
研究了亚油酸（LA）被一氧化氮衍生物硝化的内源性产物硝基亚油酸酯（LNO 2）对大鼠内皮细胞-白细胞相互作用的血管效应。共聚焦显微镜分析表明，LNO 2能够提供自由基一氧化氮（（NO）-N-中心点）进入细胞，5分钟后，其管理到培养的细胞，与释放的高峰在30分钟。THP-1单核细胞与LNO 2孵育5分钟呈现亚硝化的CD 40，导致其失活。通过活体显微镜测定在体内观察到LNO 2的其他抗炎作用。LNO 2减少肠系膜网毛细血管后微静脉中粘附的白细胞数量。除此之外，LNO 2降低了循环白细胞中2-整合素的mRNA和蛋白表达，以及从毛细血管后小静脉分离的内皮细胞中的VCAM-1，证实了其对两种细胞类型的抗粘附作用。此外，2-（4-羧基苯基）-4，4，5，5-四甲基咪唑啉-1-氧基-3-氧化物，一氧化氮清除剂，部分取消了LNO 2对白细胞-内皮细胞相互作用的抑制作用，表明LNO 2的抗粘附作用涉及双重作用，作为一氧化氮供体以及通过一氧化氮非依赖性机制。总之，LNO 2抑制粘附分子的表达，促进（NO）-N-中心点失活的CD 40-CD 40 L系统，这两个重要的炎症反应过程。(C)2010年爱思唯尔公司All rights reserved.
The vascular effects of nitrolinoleate (LNO2), an endogenous product of linoleic acid (LA) nitration by nitric oxide-derived species and a potential nitrosating agent, were investigated on rat endothelial-leukocyte interactions. Confocal microscopy analysis demonstrated that LNO2 was capable to deliver free radical nitric oxide ((NO)-N-center dot) into cells, 5 min after its administration to cultured cells, with a peak of liberation at 30 min. THP-1 monocytes incubated with LNO2 for 5 min presented nitrosation of CD40, leading to its inactivation. Other anti-inflammatory actions of LNO2 were observed in vivo by intravital microscopy assays. LNO2 decreased the number of adhered leukocytes in postcapillary venules of the mesentery network. In addition to this, LNO2 reduced mRNA and protein expression of 2-integrin in circulating leukocytes, as well as VCAM-1 in endothelial cells isolated from postcapillary venules, confirming its antiadhesive effects on both cell types. Moreover, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a nitric oxide scavenger, partially abolished the inhibitory action of LNO2 on leukocyte-endothelium interaction, suggesting that the antiadhesion effects of LNO2 involve a dual role in leukocyte adhesion, acting as a nitric oxide donor as well as through nitric oxide-independent mechanisms. In conclusion, LNO2 inhibited adhesion molecules expression and promoted (NO)-N-center dot inactivation of the CD40-CD40L system, both important processes of the inflammatory response. (C) 2010 Elsevier Inc. All rights reserved.