M1‐polarized alveolar macrophages are crucial in a mouse model of transfusion‐related acute lung injury

BACKGROUND The pathogenesis of transfusion-related acute lung injury (TRALI) progress is incompletely understood, and specific therapies for TRALI are lacking. Alveolar macrophages (AMs) are critical for initiation and resolution of lung inflammation. However, the role of AMs in the pathogenesis of TRALI-associated lung failure is poorly understood. STUDY DESIGN AND METHODS Mouse model for in vivo imaging of interleukin (IL)-6 activation in AMs was established by intratracheal instillation of a lentiviral vector carrying the luciferase reporter gene. The TRALI mouse model was produced by intraperitoneal lipopolysaccharide plus intravenous major histocompatibility complex Class I monoclonal antibody treatment. We focused on the changes in AMs in the lung during TRALI and examined whether targeting AMs is an effective strategy to alleviate this condition. MEASUREMENTS AND MAIN RESULTS We confirmed that TRALI progress is accompanied by IL-6 activation in AMs. Further study showed that AMs undergo M1 activation during TRALI progress. AM depletion protected mice from TRALI, and transfusion of M1-polarized AMs into 34-1-2 s-treated mice elevated acute lung injury, indicating that the severity of TRALI was able to be ameliorated by targeting AM polarization. Next, we showed that alpha(1)-antitrypsin (AAT) expression improved lung injury by modulating the production of IL-6 in AMs and decreased polarization of AMs toward the M1 phenotype. CONCLUSIONS M1-polarized AMs are crucial in a mouse model of TRALI, and AAT may serve as a future treatment for TRALI by regulating the polarization of AMs.