Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation
Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation
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DOI：
10.1111/j.1365-2222.2005.02231.x
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发表时间：
2005-07-01
影响因子：
6.1
通讯作者：
Chilvers, ER
中科院分区：
文献类型：
--
作者：
Brazil, TJ;Dagleish, MP;Chilvers, ER
背景中性粒细胞凋亡和吞噬细胞清除已被提出作为影响气道inflammation.Objective决议的关键决定因素，以确定在自然发生的马嗜中性粒细胞肺inflammatory.Methods和结果5小时发霉干草/稻草的挑战过敏的马引起短暂的肺功能障碍持续4天的疾病模型中的中性粒细胞引发，招聘，激活和随后的清除的动力学。在24小时，循环中性粒细胞被引发，并在体外显示延迟的自发凋亡率。空域中的中性粒细胞数量在5 h达到峰值，然后突然下降，4天后恢复到攻毒前水平。与循环细胞相比，气隙中性粒细胞表现出呼吸爆发活性增加，并且马中性粒细胞弹性蛋白酶2A浓度与中性粒细胞数量平行增加，表明体内引发和脱粒。凋亡中性粒细胞数量和吞噬凋亡中性粒细胞的肺泡巨噬细胞比例在24 h和4 d后显著增加，结论这是在自然的气道炎症疾病模型中首次证实了中性粒细胞自发凋亡和吞噬细胞清除，并提供了关键的动力学数据来支持这种清除的假设，该通路在嗜酸性炎症的消退中起核心作用。
Background Neutrophil apoptosis and phagocytic clearance have been proposed as key determinants affecting the resolution of airway inflammation.Objective To determine the kinetics of neutrophil priming, recruitment, activation and subsequent clearance in a naturally occurring equine disease model of neutrophilic pulmonary inflammation.Methods and Results A 5 h mouldy hay/straw challenge in hypersensitive horses induced transient pulmonary dysfunction lasting 4 days. At 24 h circulating neutrophils were primed and displayed delayed rates of spontaneous apoptosis in vitro. Neutrophil numbers in the airspaces peaked at 5 h and then fell abruptly, returning to pre-challenge levels by 4 days. Airspace neutrophils demonstrated increased respiratory burst activity compared with circulating cells and equine neutrophil elastase 2A concentrations increased in parallel with neutrophil numbers indicating in vivo priming and degranulation. The number of apoptotic neutrophils and proportion of alveolar macrophages containing phagocytosed apoptotic neutrophils increased significantly at 24 h and 4 days post-challenge corresponding to the period of most rapid neutrophil clearance.Conclusion This is the first demonstration of spontaneous neutrophil apoptosis and phagocytic removal in a natural disease model of airway inflammation and provides critical kinetic data to support the hypothesis that this clearance pathway plays a central role in the resolution of neutrophilic inflammation.