Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sci Adv. 2019 Aug 14;5(8):eaax3387. doi: 10.1126/sciadv.aax3387. eCollection 2019 Aug.
Pneumonia poses profound health threats to preterm infants. Alveolar macrophages (AMs) eliminate inhaled pathogens while maintaining surfactant homeostasis. As AM development only occurs perinatally, therapies that accelerate AM maturation in preterms may improve outcomes. We tested therapeutic rescue of AM development in mice lacking the actin-bundling protein L-plastin (LPL), which exhibit impaired AM development and increased susceptibility to pneumococcal lung infection. Airway administration of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to LPL neonates augmented AM production. Airway administration distinguishes the delivery route from prior human infant trials. Adult LPL animals that received neonatal GM-CSF were protected from experimental pneumococcal challenge. No detrimental effects on surfactant metabolism or alveolarization were observed. Airway recombinant GM-CSF administration thus shows therapeutic promise to accelerate neonatal pulmonary immunity, protecting against bacterial pneumonia.
肺炎对早产儿的健康构成严重威胁。肺泡巨噬细胞（AMs）在维持表面活性剂动态平衡的同时清除吸入的病原体。由于 AM 的发育仅在围产期发生，因此加速早产儿 AM 成熟的治疗方法可能会改善预后。我们在缺乏肌动蛋白结合蛋白 L 血小板（LPL）的小鼠中测试了 AM 发育的治疗性挽救，LPL 小鼠表现出 AM 发育受损和对肺炎球菌肺部感染的易感性增加。气道给予重组粒细胞-巨噬细胞集落刺激因子（GM-CSF）可增加 LPL 新生儿的 AM 产生。气道给药区分了与之前的人类婴儿试验的给药途径。接受新生儿 GM-CSF 的成年 LPL 动物可免受实验性肺炎球菌挑战的保护。未观察到对表面活性剂代谢或肺泡化的有害影响。因此，气道重组 GM-CSF 给药具有加速新生儿肺免疫的治疗潜力，可预防细菌性肺炎。
