Neutrophils and acute lung injury
Neutrophils and acute lung injury
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DOI：
10.1097/01.ccm.0000057843.47705.e8
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发表时间：
2003-04-01
影响因子：
8.8
通讯作者：
Abraham, E
中科院分区：
文献类型：
--
作者：
Abraham, E
目的：中性粒细胞是急性肺损伤（ALI）炎症反应的重要组成部分。本讨论旨在回顾中性粒细胞在ALI发生和发展中的作用，并强调在ALI背景下参与中性粒细胞活化的主要细胞内信号通路。数据来源：MEDLINE，原始研究论文和综述论文。研究选择：相关实验室和临床研究。数据提取：系统综述。数据综合：活化的中性粒细胞似乎在大多数ALI病例的发展中起核心作用。在实验模型中，中性粒细胞的消除显著降低了ALI的严重程度。此外，在伴有肺损伤的血小板减少症患者中，随着中性粒细胞减少症消退，肺功能恶化已得到充分描述。在ALI模型中，在肺中积聚的中性粒细胞表现出激酶Akt和p38的活化增加;转录调节因子核因子-κ B的核积聚增加;以及促炎细胞因子的产生增加，特别是那些其转录依赖于核因子-κ B的细胞因子。肺中中性粒细胞凋亡减少也是特征性的。抑制p38，Akt，或核因子-kappaB激活减少内毒素或血管紧张素Ⅱ诱导的ALI.Conclusions的严重程度：激活的中性粒细胞在肺部的积累是一个早期的步骤，在肺部炎症过程中，导致ALI。尽管实验模型表明中性粒细胞中p38、Akt和核因子-κ B的激活有助于ALI，但这些途径在危重患者中的相对重要性仍有待确定。然而，调节中性粒细胞中p38、Akt和核因子-κ B的活化似乎是严重ALI患者的适当治疗靶点。
Objective: Neutrophils are an important component of the inflammatory response that characterizes acute lung injury (ALI). This discussion aims to review the contribution of neutrophils to the development and progression of ALI and to highlight the major intracellular signaling pathways that are involved in neutrophil activation in the setting of ALI.Data Sources: MEDLINE, original research papers, and review papers.Study Selection: Relevant laboratory and clinical studies.Data Extraction: Systemic review.Data Synthesis: Activated neutrophils appear to play a central role in the development of most cases of ALI. In experimental models, the elimination of neutrophils markedly decreases the severity of ALI. Furthermore, in neutropenic patients with lung injury, deterioration of pulmonary function as neutropenia resolves has been well described. The neutrophils that accumulate in the lungs in models of ALI demonstrate increased activation of the kinases Akt and p38; increased nuclear accumulation of the transcriptional regulatory factor, nuclear factor-kappaB; and increased production of proinflammatory cytokines, particularly those whose transcription is dependent on nuclear factor-kappaB. Decreased apoptosis among neutrophils in the lungs is also characteristic. Inhibiting p38, Akt, or nuclear factor-kappaB activation diminishes the severity of endotoxin- or hemorrhage-induced ALI.Conclusions: The accumulation of activated neutrophils in the lungs is an early step in the pulmonary inflammatory process that leads to ALI. Although experimental models indicate that the activation of p38, Akt, and nuclear factor-kappaB in neutrophils contributes to ALI, the relative importance of these pathways in critically ill patients remains to be determined. Nevertheless, modulation of the activation of p38, Akt, and nuclear factor-kappaB in neutrophils appears to be an appropriate therapeutic target in severely ill patients with ALI.