Neutrophil granule contents in the pathogenesis of lung injury
Neutrophil granule contents in the pathogenesis of lung injury
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DOI：
10.1097/01.moh.0000190113.31027.d5
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发表时间：
2006-01-01
影响因子：
3.2
通讯作者：
Downey, GP
中科院分区：
文献类型：
--
作者：
Moraes, TJ;Zurawska, JH;Downey, GP
审查的目的。本文就中性粒细胞在急性肺损伤中的作用及其在炎症组织损伤中的作用机制作一综述。中性粒细胞产物如弹性蛋白酶、活性氧和抗微生物肽可通过激活细胞表面受体或调节信号转导途径以非降解方式改变肺细胞功能。这些影响可能对宿主有益或有害。总结。中性粒细胞在先天性免疫应答中的主要功能--遏制和杀死入侵的微生物病原体--是通过一系列快速和协调的应答来实现的，这些应答最终导致病原体的吞噬作用和细胞内杀死。中性粒细胞具有强效的抗微生物武器库，包括氧化剂、蛋白酶和阳离子肽。吞噬细胞NADPH氧化酶产生活性氧物质（例如氧气），具有杀微生物作用。中性粒细胞胞质内的颗粒含有有效的蛋白水解酶和阳离子蛋白，可以消化各种微生物底物。这些化合物直接释放到吞噬体中，将病原体和细胞毒性产物区室化。然而，在病理学情况下，杀微生物化合物不受调节地释放到细胞外空间中会自相矛盾地损害宿主组织。中性粒细胞的非特异性抑制在临床上是不现实的，因为它会使宿主易受感染。随着嗜中性粒细胞颗粒内容物的作用机制的阐明，将鉴定允许抑制嗜中性粒细胞的有害作用同时避免抑制其有益作用的治疗靶标。
Purpose of review. This review summarizes recent literature on the role of neutrophil granule contents in acute lung injury and the mechanisms by which these contribute to inflammatory tissue injury.Recent findings. Neutrophil products such as elastase, reactive oxygen species, and antimicrobial peptides can alter pulmonary cell function in a nondegradative fashion through activation of cell surface receptors or modulation of signal transduction pathways. These effects can be either beneficial or detrimental to the host.Summary. The primary function of neutrophils in the innate immune response - to contain and kill invading microbial pathogens - is achieved through a series of rapid and coordinated responses culminating in phagocytosis and intracellular killing of the pathogens. Neutrophils have a potent antimicrobial arsenal that includes oxidants, proteinases, and cationic peptides. Reactive oxygen species such as oxygen are produced by the phagocyte NADPH oxidase and are microbicidal. Granules within the neutrophil cytoplasm contain potent proteolytic enzymes and cationic proteins that can digest a variety of microbial substrates. These compounds are released directly into the phagosome, compartmentalizing both the pathogen and the cytotoxic products. Under pathological circumstances, however, unregulated release of microbicidal compounds into the extracellular space can paradoxically damage host tissues. Nonspecific inhibition of neutrophils is not clinically realistic, as it would leave the host vulnerable to infection. As the mechanisms of action of neutrophil granule contents are elucidated, therapeutic targets will be identified that will allow for suppression of neutrophils' detrimental effects while avoiding inhibition of their beneficial effects.