Targeting neutrophil apoptosis for enhancing the resolution of inflammation.
Targeting neutrophil apoptosis for enhancing the resolution of inflammation.
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DOI：
10.3390/cells2020330
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发表时间：
2013-05-22
期刊：
影响因子：
6
通讯作者：
Filep JG
中科院分区：
文献类型：
--
作者：
El Kebir D;Filep JG
急性炎症的消退是一个活跃的过程，需要抑制白细胞的进一步募集和从炎症部位去除白细胞。迁出的中性粒细胞在被清道夫巨噬细胞清除之前经历了凋亡。最近在不同炎症模型中使用各种基因敲除、转基因和药理学策略的研究证实，中性粒细胞凋亡是消解炎症的关键控制点。对死亡机制的分析揭示了中性粒细胞在执行死亡程序时的明显特征，这可以作为控制中性粒细胞寿命的靶点。事实上，从必需脂肪酸中提取的抗炎和促分解脂质介质，如脂氧素A4和Resolvin E1，金刚藤类化合物和蛋白质，如Annexin A1和TRAIL，以及细胞周期蛋白依赖的激酶抑制剂，可以通过诱导中性粒细胞凋亡和促进泡腾细胞吞噬来促进炎症的消退，从而增强炎症的消退。在这篇综述中，我们讨论了了解这些作用的分子基础的最新进展，强调了治疗性诱导中性粒细胞凋亡在抑制中性粒细胞介导的组织损伤和各种疾病潜在的炎症中的潜力。
Resolution of acute inflammation is an active process that requires inhibition of further leukocyte recruitment and removal of leukocytes from inflamed sites. Emigrated neutrophils undergo apoptosis before being removed by scavenger macrophages. Recent studies using a variety of gene knockout, transgenic and pharmacological strategies in diverse models of inflammation established neutrophil apoptosis as a critical control point in resolving inflammation. Analysis of death mechanisms revealed distinct features in executing the death program in neutrophils, which can be exploited as targets for controlling the lifespan of neutrophils. Indeed, anti-inflammatory and pro-resolution lipid mediators derived from essential fatty acids, such as lipoxin A4 and resolvin E1, autacoids and proteins, such as annexin A1 and TRAIL, and cyclin-dependent kinase inhibitors, can enhance the resolution of inflammation through induction of neutrophil apoptosis and promoting their removal by efferocytosis. In this review, we discuss recent advances in understanding the molecular basis of these actions, highlighting the potential of therapeutic induction of neutrophil apoptosis for dampening neutrophil-mediated tissue injury and inflammation underlying a variety of diseases.