title: Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice.
abstract: Abstract Exposure to amphibole asbestos has been associated with production of autoantibodies in mice and humans, and increases the risk of systemic autoimmune disease. However, epidemiological studies of chrysotile exposure have not indicated a similar induction of autoimmune responses. To demonstrate this difference in controlled exposures in mice, and to explore possible mechanistic explanations for the difference, C57BL/6 mice were exposed intratracheally to amphibole or chrysotile asbestos, or to saline only. Serum antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), serum cytokines, and immunoglobulin isotypes were evaluated 8 months after the final treatment. The percentages of lymphocyte sub-sets were determined in the spleen and lungs. The results show that amphibole, but not chrysotile, asbestos increases the frequency of ANA/ENA in mice. Amphibole and chrysotile both increased multiple serum cytokines, but only amphibole increased IL-17. Both fibers decreased IgG1, without significant changes in other immunoglobulin isotypes. Although there were no gross changes in overall percentages of T- and B-cells in the spleen or lung, there was a significant increase in the normally rare populations of suppressor B-cells (CD19(+), CD5(+), CD1d(+)) in both the spleen and lungs of chrysotile-exposed mice. Overall, the results suggest that, while there may be an inflammatory response to both forms of asbestos, there is an autoimmune response in only the amphibole-exposed, but not the chrysotile-exposed mice. These data have critical implications in terms of screening and health outcomes of asbestos-exposed populations.
authors.affiliation: Pacific Northwest University of Health Sciences, College of Osteopathic Medicine , Yakima, WA , USA and.
authors.forename: Aaron
authors.initials: A
authors.lastname: Ferro
authors.forename: Christian Nash
authors.initials: CN
authors.lastname: Zebedeo
authors.forename: Chad
authors.initials: C
authors.lastname: Davis
authors.forename: Kok Whei
authors.initials: KW
authors.lastname: Ng
authors.forename: Jean C
authors.initials: JC
authors.lastname: Pfau
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D015703:Antigens, CD / Q000378:metabolism; D017636:Asbestos, Amphibole / Q000009:adverse effects; D017632:Asbestos, Serpentine / Q000009:adverse effects; D001195:Asbestosis / Q000175:diagnosis* / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003937:Diagnosis, Differential; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007165:Immunosuppression Therapy; D019570:Inhalation Exposure; D020381:Interleukin-17 / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D008403:Mass Screening; D051379:Mice; D008810:Mice, Inbred C57BL; D019016:Mineral Fibers / Q000009:adverse effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D017636:Asbestos, Amphibole; D017632:Asbestos, Serpentine; D007074:Immunoglobulin G; D020381:Interleukin-17; D019016:Mineral Fibers
keywords: Amphibole; TH17; asbestos; autoantibodies; chrysotile; inhalation toxicology