Effects of Hyperoxia Exposure on the Polarization of Alveolar-like Macrophages in a Mouse Model of LPS-induced Lung Inflammation

Acute respiratory distress syndrome (ARDS) is a severe lung disease of high mortality (30-50%). Patients require lifesaving oxygen therapy, however hyperoxia can induce pulmonary inflammation and cellular damage. Although alveolar macrophages (AMs) are essential for lung immune homeostasis, they become compromised during inflammatory lung injury. Stem cell-derived alveolar-like macrophages (ALMs) are a prospective therapeutic for lung diseases like ARDS. Using in vitro and in vivo methods, I investigated the impacts of hyperoxia on ALMs during acute inflammation. ALMs retain their viability and antimicrobial abilities during moderate hyperoxia exposure in vitro. ALMs possess a hybrid M1/M2 phenotype that remained stable upon moderate hyperoxia exposure. After intratracheal delivery to mice, ALMs adopt further characteristics of primary AMs. Hyperoxia did not exacerbate phenotypic changes of ALMs caused by LPS-induced lung inflammation in mice. These results support the concept that ALMs may have potential benefit in human ARDS patients receiving conservative oxygen therapy.M.Sc