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-α 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.
['Désirée Boehme|Julia|J|', 'Pietkiewicz|Sabine|S|', 'Lavrik|Inna|I|', 'Jeron|Andreas|A|', 'Bruder|Dunja|D|']
D000818:Animals D001327:Autoimmune Diseases D002908:Chronic Disease D004195:Disease Models, Animal D004797:Enzyme-Linked Immunosorbent Assay D005434:Flow Cytometry D007249:Inflammation D036341:Intercellular Signaling Peptides and Proteins D008171:Lung Diseases D016676:Macrophages, Alveolar D051379:Mice D008822:Mice, Transgenic D060888:Real-Time Polymerase Chain Reaction D020133:Reverse Transcriptase Polymerase Chain Reaction D051117:Scavenger Receptors, Class A D013290:Streptococcal Infections D013296:Streptococcus pneumoniae D014409:Tumor Necrosis Factor-alpha
Alveolar macrophage Inflammation Chronic lung disease Infection Macrophage polarization