Objective: Neutrophil infiltration and release of the abundant human neutrophil peptides (HNP) are a common clinical feature in critically ill patients. We tested a hypothesis that different cell types respond to HNP differently in lung microenvironment that may influence the host responses.
Methods: Plasma concentrations of HNP were measured in healthy volunteers and patients with sepsis. Cells including the bacteria P. aeruginosa, human lung epithelial cells and mesenchymal stromal cells (MSCs) were exposed to various concentrations of HNP. Bacterial killing, epithelial cell inflammation, MSC adhesion and behaviours were examined after HNP stimulation.
Results: Incubation of P. aeruginosa or stimulation of human lung epithelial cells with HNP resulted in bacterial killing or IL-8 production at a dose of 50 μg/mL, while MSC adhesion and alternations of secretome profiles took place after HNP stimulation at a dose of 10 μg/mL. The secretome profile changes were characterized by increased release of the IL-6 family members such as C-reactive protein (CRP), leukemia inhibitory factor (LIF) and interleukin (IL-11), and first apoptosis signal (FAS) and platelet-derived growth factor-AA as compared to a vehicle control group.
Conclusion: Stimulation of MSCs with HNP resulted in changes of secretome profiles at 5-fold lower concentration than that required for bacterial killing and lung epithelial inflammation. This undisclosed risk factor of HNP in lung environment should be taken into consideration when MSCs are applied as cell therapy in inflammatory lung diseases.

Keywords: defensins, sepsis, lung injury, cytokines


中文翻译：

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人中性粒细胞肽对铜绿假单胞菌杀伤、上皮细胞炎症和间充质基质细胞分泌组谱的调节

目的：中性粒细胞浸润和丰富的人中性粒细胞肽（HNP）的释放是危重患者常见的临床特征。我们测试了一个假设，即不同细胞类型在肺微环境中对 HNP 的反应不同，这可能会影响宿主反应。
方法：测量健康志愿者和脓毒症患者的血浆 HNP 浓度。将包括细菌铜绿假单胞菌、人肺上皮细胞和间充质基质细胞 (MSCs) 在内的细胞暴露于各种浓度的 HNP。在 HNP 刺激后检查细菌杀伤、上皮细胞炎症、MSC 粘附和行为。
结果：铜绿假单胞菌的孵化或用 HNP 刺激人肺上皮细胞导致 50 μg/mL 剂量的细菌杀死或 IL-8 产生，而 10 μg/mL 剂量的 HNP 刺激后发生 MSC 粘附和分泌组谱的改变。分泌组谱变化的特征是 IL-6 家族成员的释放增加，例如 C 反应蛋白 (CRP)、白血病抑制因子 (LIF) 和白细胞介素 (IL-11)，以及第一细胞凋亡信号 (FAS) 和血小板-与载体对照组相比，衍生生长因子-AA。
结论：用 HNP 刺激 MSC 导致分泌组谱的变化，其浓度比细菌杀死和肺上皮炎​​症所需的浓度低 5 倍。在将 MSCs 用作炎症性肺病的细胞疗法时，应考虑到这一未公开的肺环境中 HNP 的危险因素。

关键词：防御素，脓毒症，肺损伤，细胞因子