Department of Surgery, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA 02215, USA.
Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia.
Int J Mol Sci. 2023 Apr 21;24(8):7627. doi: 10.3390/ijms24087627.
Nosocomial pneumonia is a leading cause of critical illness and mortality among seriously injured trauma patients. However, the link between injury and the development of nosocomial pneumonia is still not well recognized. Our work strongly suggests that mitochondrial damage-associated molecular patterns (mtDAMPs), especially mitochondrial formyl peptides (mtFPs) released by tissue injury, play a significant role in developing nosocomial pneumonia after a serious injury. Polymorphonuclear leukocytes (neutrophils, PMN) migrate toward the injury site by detecting mtFPs through formyl peptide receptor 1 (FPR1) to fight/contain bacterial infection and clean up debris. Activation of FPR1 by mtFPs enables PMN to reach the injury site; however, at the same time it leads to homo- and heterologous desensitization/internalization of chemokine receptors. Thus, PMN are not responsive to secondary infections, including those from bacteria-infected lungs. This may enable a progression of bacterial growth in the lungs and nosocomial pneumonia. We propose that the intratracheal application of exogenously isolated PMN may prevent pneumonia coupled with a serious injury.
医院获得性肺炎是严重创伤患者发生危重症和死亡的主要原因。然而，损伤与医院获得性肺炎发生之间的联系尚未被充分认识。我们的研究工作强烈提示，线粒体损伤相关分子模式（mtDAMPs），特别是组织损伤释放的线粒体衍生形式肽（mtFPs），在严重损伤后继发医院获得性肺炎的过程中发挥重要作用。多形核白细胞（中性粒细胞，PMN）通过形式肽受体 1（FPR1）检测 mtFPs 向损伤部位迁移，以抵抗/控制细菌感染和清除碎片。mtFPs 激活 FPR1 使 PMN 能够到达损伤部位；然而，与此同时，它导致趋化因子受体的同源和异源脱敏/内化。因此，PMN 对二次感染（包括来自肺部细菌感染的感染）没有反应。这可能使肺部细菌生长和医院获得性肺炎进展。我们提出，气管内应用分离的外源性 PMN 可能预防与严重损伤相关的肺炎。
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