Differential polarization of alveolar macrophages and bone marrow-derived monocytes following chemically and pathogen-induced chronic lung inflammation

• Published in: Journal of leukocyte biology Vol. 88; no. 1; pp. 159 - 168
• Main Authors: Redente, Elizabeth F., Higgins, David M., Dwyer-Nield, Lori D., Orme, Ian M., Gonzalez-Juarrero, Mercedes, Malkinson, Alvin M.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.07.2010; The Society for Leukocyte Biology
• Subjects: Animals; Bone Marrow Cells - cytology; butylated hydroxytoluene; Butylated Hydroxytoluene - toxicity; Cell Polarity; Chronic Disease; IFN‐γ; IL‐4; Inflammation, Extracellular Mediators, & Effector Molecules; Interferon-gamma - biosynthesis; Interleukin-4 - biosynthesis; Macrophages, Alveolar - physiology; Male; Mice; Mice, Inbred C57BL; Monocytes - physiology; Pneumonia - immunology; tuberculosis; Tuberculosis - immunology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0609378

Alveolar macrophages undergo similar polarization to chemically and pathogen‐induced chronic lung inflammation, but the phenotype of bone marrow‐derived monocytes varies between inflammations. Alveolar macrophages and BDMCs undergo sequential biochemical changes during the chronic inflammatory response to chemically induced lung carcinogenesis in mice. Herein, we examine two chronic lung inflammation models—repeated exposure to BHT and infection with Mycobacterium tuberculosis—to establish whether similar macrophage phenotype changes occur in non‐neoplastic pulmonary disease. Exposure to BHT or M. tuberculosis results in pulmonary inflammation characterized by an influx of macrophages, followed by systemic effects on the BM and other organs. In both models, pulmonary IFN‐γ and IL‐4 production coincided with altered polarization of alveolar macrophages. Soon after BHT administration or M. tuberculosis infection, IFN‐γ content in BALF increased, and BAL macrophages became classically (M1) polarized, as characterized by increased expression of iNOS. As inflammation progressed in both models, the amount of BALF IFN‐γ content and BAL macrophage iNOS expression decreased, and BALF IL‐4 content and macrophage arginase I expression rose, indicating alternative/M2 polarization. Macrophages present in M. tuberculosis‐induced granulomas remained M1‐polarized, implying that these two pulmonary macrophage populations, alveolar and granuloma‐associated, are exposed to different activating cytokines. BDMCs from BHT‐treated mice displayed polarization profiles similar to alveolar macrophages, but BDMCs in M. tuberculosis‐infected mice did not become polarized. Thus, only alveolar macrophages in these two models of chronic lung disease exhibit a similar progression of polarization changes; polarization of BDMCs was specific to BHT‐induced pulmonary inflammation, and polarization of granuloma macrophages was specific to the M. tuberculosis infection.