Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109-5033, USA.
J Trauma Acute Care Surg. 2012 Mar;72(3):614-22; discussion 622-3. doi: 10.1097/TA.0b013e318243d9b1.
Lung contusion (LC) induces inflammation with high local concentrations of proinflammatory mediators stimulating chemotaxis and activation of neutrophils. LC is also a risk factor for development of pneumonia; however, the reason for this increased susceptibility is not clearly identified. We hypothesize that LC creates acute changes in the host pulmonary innate immune system that leads to vulnerability from a "second" hit bacterial infection.
Female C57Bl/6 mice underwent LC injury at time -6 hours. At 0 hours, these mice were inoculated intratracheally with 1,000 colony forming unit (CFU) of Klebsiella pneumoniae (LC+Pneu) or vehicle (LC). Control animals underwent a sham LC injury followed by pneumonia (Sham+Pneu). Bronchoalveolar lavage (BAL) fluid and lung tissue specimens were collected. Lung bacteria levels were quantified by serial dilution, plating, and counting CFUs. Cytokine levels were assayed by ELISA. Cell type identification and quantification was performed using flow cytometry.
Survival at 72 hours was markedly different for the LC, Sham+Pneu, and LC+Pneu groups (100%, 80%, 20%, p < 0.05 Sham+Pneu vs. LC+Pneu). LC+Pneu animals had decreased pulmonary bacterial clearance at 24 hours compared with the Sham+Pneu group (4 × 10(7) vs. 8 × 10(6) CFUs, p < 0.05). BAL levels of IL-1β, IL-6, and keratinocyte chemoattractant were all significantly elevated in LC+Pneu mice compared with the Sham+Pneu group at 24 hours. Conversely, the Sham+Pneu mice had increased levels of macrophage inflammatory protein-2, total cells, macrophages, and neutrophils in BAL compared with the LC+Pneu group at 24 hours. LC+Pneu animals demonstrated changes in macrophage apoptosis and necrosis in BAL samples obtained 2 hours after induction of pneumonia when compared with the Sham+Pneu group. Both Sham+Pneu and LC+Pneu animals demonstrated an increase in the level of IL-10 in BAL fluid compared with LC animals.
Acute inflammation after LC acts to modulate the presence of inflammatory cells necessary to combat gram-negative bacteria. This results in decreased bacterial clearance and increased mortality from pneumonia.
肺挫伤（LC）会引发炎症，局部促炎介质浓度升高会刺激趋化作用和中性粒细胞的激活。LC 也是肺炎发生的一个危险因素；然而，这种易感性增加的原因尚不清楚。我们假设 LC 会导致宿主肺部固有免疫系统发生急性变化，从而使其易受“二次”细菌感染的影响。
雌性 C57Bl/6 小鼠在-6 小时时发生 LC 损伤。在 0 小时时，这些小鼠通过气管内接种 1000 个菌落形成单位（CFU）的肺炎克雷伯菌（LC+Pneu）或载体（LC）。对照动物接受假 LC 损伤，然后发生肺炎（Sham+Pneu）。收集支气管肺泡灌洗液（BAL）和肺组织标本。通过连续稀释、平板培养和计数 CFU 来定量肺内细菌水平。通过 ELISA 测定细胞因子水平。使用流式细胞术进行细胞类型鉴定和定量。
72 小时的存活率在 LC、Sham+Pneu 和 LC+Pneu 组之间有明显差异（100%、80%、20%，p<0.05 Sham+Pneu 与 LC+Pneu 比较）。与 Sham+Pneu 组相比，LC+Pneu 动物在 24 小时时肺内细菌清除率降低（4×10(7)与 8×10(6)CFUs，p<0.05）。与 Sham+Pneu 组相比，LC+Pneu 小鼠在 24 小时时 BAL 中的 IL-1β、IL-6 和角质细胞趋化因子水平均显著升高。相反，与 LC+Pneu 组相比，Sham+Pneu 组在 24 小时时 BAL 中的巨噬细胞炎症蛋白-2、总细胞、巨噬细胞和中性粒细胞水平升高。与 Sham+Pneu 组相比，LC+Pneu 动物在诱导肺炎后 2 小时时 BAL 样本中观察到巨噬细胞凋亡和坏死的变化。与 LC 动物相比，Sham+Pneu 和 LC+Pneu 动物的 BAL 液体中的 IL-10 水平均升高。
LC 后急性炎症会调节对抗革兰氏阴性菌所需的炎症细胞的存在。这导致细菌清除率降低和肺炎死亡率增加。
