Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

低氧血症是急性呼吸窘迫综合征 (ARDS) 的一个典型特征，ARDS 是肺部或全身炎症的一种常见致命并发症，但由此产生的组织缺氧及其对免疫反应的影响却常常被忽视。在本研究中，我们发现 ARDS 患者在通气的前 48 小时内出现低氧血症和单核细胞减少。在缺氧急性肺损伤的小鼠模型中也观察到单核细胞减少症，其中低氧血症导致骨髓中 I 型干扰素信号传导的抑制。这种受损的单核细胞生成导致单核细胞衍生的巨噬细胞积累减少，并增强中性粒细胞介导的肺部炎症。对缺氧性肺损伤的小鼠给予集落刺激因子1可挽救单核细胞减少症，改变循环单核细胞的表型，增加肺中单核细胞衍生的巨噬细胞并限制损伤。因此，组织缺氧改变了免疫反应的动态，对宿主造成损害，而解决异常反应的干预措施为 ARDS 提供了新的治疗策略。