Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Eur J Clin Invest. 2012 Dec;42(12):1342-9. doi: 10.1111/j.1365-2362.2012.02720.x. Epub 2012 Sep 18.
Neutrophils are the most abundant circulating white cell in humans and play a crucial role in the innate immune response. Accumulation and activation of neutrophils, together with delayed clearance, have been shown to be a key event in the pathogenesis of acute lung injury. Previously, it has been proposed that there is substantial pooling of neutrophils within the pulmonary vasculature, even under physiological conditions, making the lung especially vulnerable to neutrophil-mediated tissue injury. However, more recent evidence suggests that only primed neutrophils accumulate in the pulmonary vasculature. This article examines the evidence for these two opposing views and proposes a new two-step model for the recruitment of neutrophils into the lung. Firstly, neutrophils that become primed, by exposure to a range of inflammatory mediators or physicochemical perturbations, become shape changed and stiff because of alterations in their cytoskeleton, and as a result, accumulate within the pulmonary circulation. In the absence of further stimuli, the healthy pulmonary vasculature is able to selectively retained these primed cells, allow them to 'de-prime' and be released back into the circulation in a quiescent, state. If this pulmonary 'de-priming' mechanism fails, or a second insult occurs, such as ventilator-associated barotrauma, which causes loss of alveolar integrity, primed neutrophils migrate from the pulmonary vasculature into the interstitial space with resultant lung injury. This canonical 'two step' model highlights the importance of neutrophil priming in the genesis of lung injury and the importance of adopting strategies to minimise alveolar injury.
中性粒细胞是人体循环中最丰富的白细胞，在先天免疫反应中发挥着至关重要的作用。积累和激活中性粒细胞，加上清除延迟，已被证明是急性肺损伤发病机制中的一个关键事件。此前，有人提出，中性粒细胞在肺血管内大量积聚，即使在生理条件下也是如此，这使得肺部特别容易受到中性粒细胞介导的组织损伤。然而，最近的证据表明，只有被激活的中性粒细胞才会积聚在肺血管内。本文研究了这两种相反观点的证据，并提出了一种新的两步模型来解释中性粒细胞向肺部的募集。首先，暴露于一系列炎症介质或物理化学干扰因素的中性粒细胞会因细胞骨架的改变而发生形态改变和变硬，从而变得僵硬，并且由于这些改变，它们在肺循环中积聚。在没有进一步刺激的情况下，健康的肺血管系统能够选择性地保留这些被激活的细胞，使它们“去激活”并以静止状态重新回到循环中。如果这个肺部的“去激活”机制失效，或者发生第二次打击，如呼吸机相关性气压伤，导致肺泡完整性丧失，激活的中性粒细胞从肺血管迁移到间质空间，导致肺损伤。这个经典的“两步”模型强调了中性粒细胞激活在肺损伤发生中的重要性，以及采取策略来最小化肺泡损伤的重要性。
