Mitochondrial damage-associated molecular patterns released by abdominal trauma suppress pulmonary immune responses.
Mitochondrial damage-associated molecular patterns released by abdominal trauma suppress pulmonary immune responses.
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DOI：
10.1097/ta.0000000000000220
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发表时间：
2014-05
期刊：
影响因子：
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通讯作者：
Hauser CJ
中科院分区：
文献类型：
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作者：
Zhao C;Itagaki K;Gupta A;Odom S;Sandler N;Hauser CJ
历史上，创伤后的发热、肺炎和脓毒症被归因于疼痛和肺厕所不良。然而，没有证据支持这种说法，也没有已知的生物学机制将损伤与感染联系起来。我们的研究表明，受损组织释放线粒体（MT）。然而，线粒体病原体相关分子模式（mtDAMP）可以模拟细菌病原体相关危险分子（PAMP）并吸引中性粒细胞（PMN）。我们假设来自创伤组织的mtDAMPs将中性粒细胞从肺部转移，导致感染易感性。麻醉大鼠（6-10只/组）通过胸部叩击进行肺挫伤（PC）。模拟创伤性MT释放，一些大鼠具有从肝脏分离的MT（等于5%肝坏死），腹膜内注射（IPMT）。阴性对照具有PC加缓冲液IP。阳性对照进行PC加盲肠结扎和穿刺（CLP）。16 h行支气管肺泡灌洗和腹腔灌洗。测定支气管和腹腔灌洗液（BALF、PLF）中的PMN计数、白蛋白、IL-β和CINC-1。将测定标准化为BUN以计算绝对浓度。PC引起肺泡IL-1β和CINC的产生以及BALF中性粒细胞增加34倍。正如预期的那样，IPMT增加了腹膜IL-1β和CINC，并将PMN吸引到腹部。但PC后IPMT可明显减少BALF中细胞因子的积聚，减少BALF中PMN的数量。CLP对BALF中性粒细胞无直接影响，但与IPMT一样，PC后BALF白细胞增多。创伤引起的mtDAMPs和腹膜感染引起的PAMPs减少了PMN在挫伤肺中的积聚，而不是作为“第二次打击”来增强PMN介导的肺损伤。这可能会使肺部易患肺炎。该范例提供了钝性组织创伤、全身性炎症和肺炎之间关系的新的机制模型，可以对其进行研究以改善创伤结果。
Historically fever, pneumonia and sepsis after trauma are ascribed to pain and poor pulmonary toilet. No evidence supports that assertion however, and no known biologic mechanisms link injury to infection. Our studies show injured tissues release mitochondria (MT). Mitochondrial danger-associated molecular patterns (mtDAMPs) however, can mimic bacterial pathogen-associated danger molecules (PAMPs) and attract neutrophils (PMN). We hypothesized mtDAMPs from traumatized tissue divert neutrophils from the lung, causing susceptibility to infection. Anesthetized rats (6–10/group) underwent pulmonary contusion (PC) by chest percussion. Modeling traumatic MT release, some rats had MT isolated from liver (equal to 5% liver necrosis) injected intra-peritoneal (IPMT). Negative controls had PC plus buffer IP. Positive controls underwent PC plus cecal ligation and puncture (CLP). At 16h bronchoalveolar and peritoneal lavages were performed. Bronchial and peritoneal lavage fluids (BALF, PLF) were assayed for PMN count, albumin, IL-β and CINC-1. Assays were normalized to BUN to calculate absolute concentrations. PC caused alveolar IL-1β and CINC production and a 34-fold increase in BALF neutrophils. As expected, IPMT increased peritoneal IL-1β and CINC and attracted PMN to the abdomen. But remarkably, IPMT after PC attenuated BALF cytokine accumulation and decreased BALF PMN. CLP had no direct effect on BALF PMNs, but like IPMT blunted BALF leukocytosis after PC. Rather than acting as a 'second hit' to enhance PMN-mediated lung injury, mtDAMPs from trauma and PAMPs from peritoneal infection diminish PMN accumulation in contused lung. This may make the lung susceptible to pneumonia. This paradigm provides a novel mechanistic model of the relationship between blunt tissue trauma, systemic inflammation and pneumonia that can be studied to improve trauma outcomes.