Alveolar macrophage depletion increases the severity of acute inflammation following nonlethal unilateral lung contusion in mice.
Alveolar macrophage depletion increases the severity of acute inflammation following nonlethal unilateral lung contusion in mice.
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DOI：
10.1097/ta.0000000000000163
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发表时间：
2014-04
期刊：
影响因子：
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通讯作者：
Raghavendran K
中科院分区：
文献类型：
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作者：
Machado-Aranda D;V Suresh M;Yu B;Dolgachev V;Hemmila MR;Raghavendran K
肺挫伤(LC)是一种常见的胸部钝性损伤。LC是发生急性肺损伤、成人呼吸窘迫综合征和呼吸机相关性肺炎的重要危险因素，所有这些都会增加创伤死亡率。LC产生一种非特异性免疫细胞反应。众所周知，中性粒细胞重新聚集会增加LC期间炎症的严重程度。然而，巨噬细胞在调节LC反应中的确切作用还没有得到很好的描述。采用皮质挫伤冲击器建立小鼠单侧LC模型。对这些动物进行胸部微型计算机断层扫描，以记录LC术后一段时间内的放射学变化。为了了解巨噬细胞在LC中的作用，在创伤前使用氯屈膦酸盐脂质体来耗尽巨噬细胞水平。通过测量压力-体积力学；定量测定白细胞、白蛋白和细胞因子的支气管肺泡灌洗水平；最后在损伤后5、24、48和72小时检查肺标本的组织病理学，评估LC后的急性炎症属性。LC后肺泡巨噬细胞数量明显减少，恢复缓慢。同时，支气管肺泡灌洗液中中性粒细胞计数显著增加。巨噬细胞的丢失可归因于细胞的凋亡和坏死。氯屈膦酸盐预治疗增加了肺部炎症的严重程度，表现为肺顺应性恶化，肺通透性增加，中性粒细胞募集放大，以及早期促炎细胞因子水平增加。调节性肺泡巨噬细胞的存在在LC后急性炎症的发病机制中起重要作用。
Lung contusion (LC) is a common injury resulting from blunt thoracic trauma. LC is an important risk factor for the development acute lung injury, adult respiratory distress syndrome, and ventilator-associated pneumonia, all of which increase mortality from trauma. LC produces a nonspecific immune cellular response. Neutrophil recruitment is known to increase the severity of inflammation during LC. However, the exact role of macrophages in modulating the response to LC has not been well described. We used a cortical contusion impactor to induce unilateral LC in mice. Thoracic micro computed tomographic scans of these animals were obtained to document radiologic changes over time following LC. To understand the role of macrophages during LC, liposomal clodronate was used to deplete macrophage levels before traumatic insult. Acute inflammatory attributes after LC were assessed, by measuring pressure-volume mechanics; quantifying bronchial alveolar lavage levels of leukocytes, albumin, and cytokines; and finally examining lung specimen histopathology at 5, 24, 48, and 72 hours after injury. After LC, alveolar macrophage numbers were significantly reduced and exhibited slowed recovery. Simultaneously, there was a significant increase in bronchial alveolar lavage neutrophil counts. The loss of macrophages could be attributed to both cellular apoptosis and necrosis. Pretreatment with clodronate increased the severity of lung inflammation as measured by worsened pulmonary compliance, increased lung permeability, amplification of neutrophil recruitment, and increases in early proinflammatory cytokine levels. The presence of regulatory alveolar macrophages plays an important role in the pathogenesis of acute inflammation following LC.