title: Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure.
abstract: Silica inhalation results in chronic lung inflammation and fibrosis. While the role of the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology, the etiology is not completely understood. Evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. In order to study the effects of crystalline silica on the APC activity of pulmonary macrophages, mice were exposed intranasally and changes in pulmonary macrophage populations were assessed using flow cytometry. Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers (MHC class II, CD11c). In addition, an in vitro system using bone marrow-derived macrophages (BMDM) was generated to assess the effects of silica on the APC activity of macrophages in vitro. Data using BMDM in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO(2)). Using a combination of in vivo and in vitro experiments, the current study describes a significant increase in an interstitial macrophage subset with an APC phenotype, as well as an increase in the APC activity of both AM and BMDM, as a direct result of exposure to crystalline silica. These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis.
authors.affiliation: Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, University of Montana, 155 Skaggs Building, Missoula, MT 59812, USA. christopher.migliaccio@umontana.edu
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Migliaccio
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Hamilton
authors.forename: Andrij
authors.initials: A
authors.lastname: Holian
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D045604:Extracellular Fluid / Q000166:cytology; D005434:Flow Cytometry; D066298:In Vitro Techniques; D019570:Inhalation Exposure / Q000009:adverse effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D012822:Silicon Dioxide