Pulmonary macrophage subpopulations in the induction and resolution of acute lung injury

• Published in: American journal of respiratory cell and molecular biology Vol. 47; no. 4; pp. 417 - 426
• Main Authors: Johnston, Laura K, Rims, Cliff R, Gill, Sean E, McGuire, John K, Manicone, Anne M
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01-10-2012
• Subjects: Acute Lung Injury - immunology; Acute Lung Injury - microbiology; Acute Lung Injury - pathology; Animals; Biomarkers - metabolism; Cell Polarity; Cell Separation; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Female; Flow Cytometry; Gene Expression Regulation; Macrophage Activation; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; Macrophages, Alveolar - physiology; Male; Mice; Mice, Inbred C57BL; Phenotype; Pneumonia, Bacterial - immunology; Pneumonia, Bacterial - microbiology; Pneumonia, Bacterial - pathology; Pseudomonas aeruginosa; Pseudomonas Infections - immunology; Pseudomonas Infections - microbiology; Pseudomonas Infections - pathology; Pulmonary Alveoli - immunology; Pulmonary Alveoli - metabolism; Pulmonary Alveoli - pathology; Transcriptome
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2012-0090oc

Macrophages are key orchestrators of the inflammatory and repair responses in the lung, and the diversity of their function is indicated by their polarized states and distinct subpopulations and localization in the lung. Here, we characterized the pulmonary macrophage populations in the interstitial and alveolar compartments during the induction and resolution of acute lung injury induced by Pseudomonas aeruginosa infection. We identified macrophage subpopulations and polarity according to FACS analysis of cell surface protein markers, combined with cell sorting for gene expression using real-time PCR. With these techniques, we validated a novel, alternatively activated (M2) marker (transferrin receptor), and we described three interstitial and alveolar macrophage subpopulations in the lung whose distribution and functional state evolved from the induction to resolution phases of lung injury. Together, these findings indicate the presence and evolution of distinct macrophage subsets in the lung that serve specific niches in regulating the inflammatory response and its resolution. Alterations in the balance and function of these subpopulations could lead to nonresolving acute lung injury.