Therapeutic characteristics of alveolar-like macrophages in mouse models of hyperoxia and LPS-induced lung inflammation

Acute respiratory distress syndrome (ARDS) is a severe lung disease of high mortality (30-50%). Patients require lifesaving supplemental 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. To combat this, stem cell-derived alveolar-like macrophages (ALMs) are a prospective therapeutic for lung diseases like ARDS. Using in vitro and in vivo approaches, we investigated the impact of hyperoxia on murine ALMs during acute inflammation. In vitro, ALMs retained their viability, growth, and antimicrobial abilities when cultured at 60% O-2, whereas they die at 90% O2. In contrast, ALMs instilled in mouse lungs remained viable during exposure of mice to 90% O-2. The ability of the delivered ALMs to phagocytose Pseudomonas aeruginosa was not impaired by exposure to 60 or 90% O-2. Furthermore, ALMs remained immunologically stable in a murine model of LPS-induced lung inflammation when exposed to 60 and 90% O-2 and effectively attenuated the accumulation of CD11b(+) inflammatory cells in the airways. These results support the potential use of ALMs in patients with ARDS receiving supplemental oxygen therapy.