Alveolar macrophages inhibit emphysematous pathology via expression of carbonic anhydrase 4.

Therapies to treat COPD remain limited and fail to prevent disease progression. Alveolar macrophages (AMs) reside in the alveoli of the lung and are ideally positioned to encounter inhaled particles and pathogens.

Despite exposure to these stimuli, AMs exhibit specialized phenotypes that restrict inflammation to prevent alveolar damage. Here we demonstrate that AMs express high levels of the surface bound enzyme carbonic anhydrase 4 (Car4). Deletion of Car4 on AMs results in increased susceptibility to emphysematous pathology and therapeutic treatment with Car4 is sufficient to prevent emphysema-like disease.