Department Surgery, Washington University School of Medicine, St Louis, Missouri, USA.
Shock. 2012 Jun;37(6):629-33. doi: 10.1097/SHK.0b013e31824ee551.
Pulmonary contusion is a major cause of respiratory failure in trauma patients. This injury frequently leads to immune suppression and infectious complications such as pneumonia. The mechanism whereby trauma leads to an immune-suppressed state is poorly understood. To further study this phenomenon, we developed an animal model of pulmonary contusion (PC) complicated by pneumonia and assessed the effect of PC and pneumonia on toll-like receptor expression in alveolar macrophages. Using a mouse model, PC was induced on the right lung, and pneumonia was induced with Pseudomonas aeruginosa (Pa) injected intratracheally 48 h after injury. Susceptibility to pneumonia was assessed by mortality at 7 days. Uninjured animals were used as controls. Bronchoalveolar lavage fluid and blood were assayed 48 h after injury and 24 h after Pa instillation to look at markers of systemic inflammation. Toll-like receptor expression in the initial inflammatory response was analyzed by flow cytometry. Unexpectedly, injured animals subjected to intratracheal injection of Pa at 48 h after PC demonstrated increased survival compared with uninjured animals. Bronchoalveolar lavage cytokine expression was increased significantly after Pa administration but not after PC alone. Toll-like receptor 4 expression on alveolar macrophages was significantly elevated in the injured group compared with sham but not in neutrophils. Animals subjected to PC are more resistant to mortality from infection with Pa and display an enhanced cytokine response when subsequently subjected to Pa. Increased expression of toll-like receptor 4 on alveolar macrophages and enhanced innate immunity are a possible mechanism of increased cytokine production and decreased susceptibility to pneumonia.
肺挫伤是创伤患者发生呼吸衰竭的主要原因。这种损伤常常导致免疫抑制和感染并发症，如肺炎。创伤导致免疫抑制状态的机制尚未完全明了。为了进一步研究这一现象，我们建立了一个伴有肺炎的肺挫伤动物模型，并评估了肺挫伤和肺炎对肺泡巨噬细胞 Toll 样受体表达的影响。我们使用小鼠模型，对右肺进行肺挫伤，在损伤后 48 小时经气管内注射铜绿假单胞菌（Pa）以诱导肺炎。通过 7 天后的死亡率来评估肺炎的易感性。未受伤的动物用作对照。在损伤后 48 小时和 Pa 注入后 24 小时采集支气管肺泡灌洗液和血液，以检测全身炎症标志物。通过流式细胞术分析初始炎症反应中 Toll 样受体的表达。出乎意料的是，与未受伤的动物相比，在肺挫伤后 48 小时经气管内注射 Pa 的受伤动物的存活率增加。在 Pa 给药后，支气管肺泡灌洗液中的细胞因子表达显著增加，但单独给予 PC 后则没有。与假手术组相比，受伤组肺泡巨噬细胞上的 Toll 样受体 4 表达显著升高，但中性粒细胞中则没有。接受 PC 的动物对 Pa 感染的死亡率较低，并且在随后受到 Pa 感染时表现出增强的细胞因子反应。肺泡巨噬细胞上 Toll 样受体 4 的表达增加和固有免疫增强可能是细胞因子产生增加和肺炎易感性降低的一种机制。
