Pulmonary macrophage subpopulations in the induction and resolution of acute lung injury.
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.
Center for Lung Biology, University of Washington, 815 Mercer Street, Seattle, WA 98109, USA.
Laura K
LK
Johnston
Cliff R
CR
Rims
Sean E
SE
Gill
John K
JK
McGuire
Anne M
AM
Manicone
D055371:Acute Lung Injury / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016764:Cell Polarity; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
D015415:Biomarkers; D016207:Cytokines