title: Innate immune processes are sufficient for driving silicosis in mice.
abstract: The lung is constantly exposed to potentially pathogenic particles and microorganisms. It has become evident recently that not only innate but also adaptive immune responses to particulates, such as SiO(2) entering the respiratory tract, are complex and dynamic events. Although the cellular mechanisms and anatomical consequences involved in the development of silicosis have been studied extensively, they still remain poorly understood. Based on their capacity for immune regulation, lymphocytes may play a key role in the respiratory response to environmental challenge by SiO(2). The objective of this study was to characterize the impact of SiO(2) exposure on respiratory immune processes, with particular emphasis on evaluating the importance of lymphocytes in the murine silicosis model. Therefore, lymphopenic mice, including NK-deficient, Rag1(-/-), or a combination (Rag1(-/-) NK-depleted), were used and demonstrated that SiO(2)-induced fibrosis and inflammation can occur independently of T, B, NK T, and NK cells. Studies in Rag1(-/-) mice suggest further that lymphocytes may participate in the regulation of SiO(2)-induced inflammation through modulation of the Nalp3 inflammasome. This observation may have clinical relevance in the treatment of inflammatory and fibrotic lung diseases that are refractory or respond suboptimally to current therapeutics.
authors.affiliation: University of Montana, Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences, Skaggs Building, Room 285A, Missoula, MT 59812-1552, USA. celine.beamer@umontana.edu
authors.forename: Celine A
authors.initials: CA
authors.lastname: Beamer
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Migliaccio
authors.forename: Forrest
authors.initials: F
authors.lastname: Jessop
authors.forename: Melanie
authors.initials: M
authors.lastname: Trapkus
authors.forename: Dorothy
authors.initials: D
authors.lastname: Yuan
authors.forename: Andrij
authors.initials: A
authors.lastname: Holian
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D011658:Pulmonary Fibrosis / Q000150:complications / Q000276:immunology / Q000473:pathology; D012822:Silicon Dioxide / Q000008:administration & dosage; D012829:Silicosis / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012822:Silicon Dioxide