Morphological and Functional Alterations of Alveolar Macrophages in a Murine Model of Chronic Inflammatory Lung Disease

Purpose Chronic lung inflammation commonly induces a multitude of structural and functional adaptations within the lung tissue and airspaces. Yet the impact of a persistent inflammatory environment on alveolar macrophages is still incompletely understood. Here, we examined morphology and function of alveolar macrophages in a transgenic mouse model of chronic lung disease. Methods Imaging flow cytometry, flow cytometry, and microscopic evaluation of alveolar macrophages isolated from healthy and inflamed lungs were performed. Gene expression of polarization markers was compared by quantitative real-time RT-PCR. The pro-inflammatory immune response of alveolar macrophages toward bacterial ligands was assessed in in vivo clodronate-liposome depletion studies. Results Chronic lung inflammation is associated with a substantially altered, activated alveolar macrophage morphology, and blunted TNF-alpha response by these cells following stimulation with ligands derived from the respiratory pathogen Streptococcus pneumoniae. Conclusions These results demonstrate pleiotropic effects of pulmonary inflammation on alveolar macrophage phenotype and function and suggest a functional impairment of these cells during infection with airborne pathogens.