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-gamma and
IL-4 production coincided with altered polarization of alveolar macrophages. Soon after
BHT administration or M.
tuberculosis infection, IFN-gamma 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-gamma 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.