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The IL‐4Rα pathway in macrophages and its potential role in silica‐induced pulmonary fibrosis
Author(s) -
Migliaccio Christopher T.,
Buford Mary C.,
Jessop Forrest,
Holian Andrij
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0807533
Subject(s) - silicosis , macrophage , pulmonary fibrosis , in vivo , biology , immunology , fibrosis , population , inflammation , in vitro , immunity , stimulation , microbiology and biotechnology , immune system , pathology , biochemistry , medicine , endocrinology , environmental health
Crystalline silica exposure can result in pulmonary fibrosis, where the pulmonary macrophage is key as a result of its ability to react to silica particles. In the mouse silicosis model, there is initial Th1‐type inflammation, characterized by TNF‐α and IFN‐γ. Previous studies determined that Th2 mediators (i.e., IL‐13) are vital to development of pulmonary fibrosis. The present study, using in vivo and in vitro techniques, compares silica exposures between Balb/c and Th2‐deficient mice in an effort to determine the link between Th2 immunity and silicosis. In long‐term experiments, a significant increase in fibrosis and activated interstitial macrophages was observed in Balb/c but not IL‐4Rα −/− mice. Additionally, a significant increase in Ym1 mRNA levels, a promoter of Th2 immunity, was determined in the interstitial leukocyte population of silica‐exposed Balb/c mice. To elucidate the effects of silica on macrophage function, bone marrow‐derived macrophages (BMdM) were exposed to particles and assayed for T cell (TC) stimulation activity. As a control, Ym1 mRNA expression in Balb/c BMdM was determined using IL‐4 stimulation. In the in vitro assay, a significant increase in TC activation, as defined by surface markers and cytokines, was observed in the cultures containing the silica‐exposed macrophages in wild‐type and IL‐4Rα −/− mice, with one exception: IL‐4Rα −/− BMdM were unable to induce an increase in IL‐13. These results suggest that crystalline silica alters cellular functions of macrophages, including activation of TC, and that the increase in Th2 immunity associated with silicosis is via the IL‐4Rα‐Ym1 pathway.