Mechanism of neutrophil recruitment to the lung after pulmonary contusion.
Mechanism of neutrophil recruitment to the lung after pulmonary contusion.
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DOI：
10.1097/shk.0b013e3182144a50
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Yoza BK
中科院分区：
文献类型：
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作者：
Hoth JJ;Wells JD;Hiltbold EM;McCall CE;Yoza BK
钝性胸部创伤导致的肺挫伤是一种常见的但知之甚少的损伤。我们以前证明肺挫伤激活局部和全身先天免疫机制，并招募中性粒细胞受伤的肺。我们推测中性粒细胞的先天免疫和炎症激活可能在肺损伤的反应中起重要作用。为了研究这一点，我们在小鼠中使用了一种肺挫伤模型，该模型与临床上在人类中观察到的模型相似，并评估了损伤后肺功能和肺中性粒细胞募集。在有和没有中性粒细胞耗竭的损伤小鼠之间进行比较。我们进一步研究了趋化因子和粘附受体在中性粒细胞募集到损伤肺中的作用。我们发现肺挫伤后肺损伤和由此产生的生理功能障碍依赖于肺泡腔内中性粒细胞的存在。我们发现，CXCL 1，CXCL 2/3，和CXCR 2参与中性粒细胞募集到肺损伤后，ICAM-1的局部表达，并积极参与这一过程。受损的gp 91 phox缺陷小鼠表现出改善的肺功能，表明中性粒细胞NADPH氧化酶介导的氧化剂生产挫伤后肺功能障碍。这些数据表明，肺挫伤后肺损伤需要中性粒细胞的存在和功能。
Blunt chest trauma resulting in pulmonary contusion is a common but poorly understood injury. We previously demonstrated that lung contusion activates localized and systemic innate immune mechanisms and recruits neutrophils to the injured lung. We hypothesized that the innate immune and inflammatory activation of neutrophils may figure prominently in the response to lung injury. To investigate this, we used a model of pulmonary contusion in the mouse that is similar to that observed clinically in humans and evaluated postinjury lung function and pulmonary neutrophil recruitment. Comparisons were made between injured mice with and without neutrophil depletion. We further examined the role of chemokines and adhesion receptors in neutrophil recruitment to the injured lung. We found that lung injury and resultant physiological dysfunction after contusion was dependent upon the presence of neutrophils in the alveolar space. We show that CXCL1, CXCL2/3, and CXCR2 are involved in neutrophil recruitment to the lung after injury, and that ICAM-1 is locally expressed and actively participates in this process. Injured gp91phox deficient mice showed improved lung function, indicating that oxidant production by neutrophil NADPH oxidase mediates lung dysfunction after contusion. These data suggest that both neutrophil presence and function are required for lung injury after lung contusion.