Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice

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.

Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

“…In previous studies, chrysotile has not been shown to produce elevated autoantibodies in humans (Birch et al, 2012) or mice (Ferro et al 2013). Chrysotile also did not induce increased serum cytokines other than IL-6, while Libby 6-Mix induced both IL-17 and IL-6 (Ferro et al 2013).…”

“…Tremolite, an amphibole asbestos, was used to compare with erionite to determine if erionite evokes similar responses by the immune cells. Chrysotile, a different type of asbestos that does not seem to promote autoimmunity (Birch et al 2012; Ferro et al 2013), was also used in this study. The cytokine data are presented as a ratio of the concentration values obtained from the treated cultures to the concentrations values of the untreated control showing the relative changes from the control values.…”

“…The mice used were female wild type C57BL/6 (Idaho State University Animal Care Facility, breeders from Jackson Labs, Bar Harbor, Maine). This strain is not genetically predisposed to systemic autoimmune responses, and was chosen in order to a) test the autoimmune responses in a genetic background that did not already produce disease, and b) to be able to compare to other published studies of ANA in mice (Pfau et al 2008; Ferro et al 2013). These mice were housed under specific pathogen free (SPF) conditions in ventilated cages (Tecniplast, West Chester, PA) with 12 hour light-dark cycle, constant temperature (22°C) and humidity (45%), and ad libitum food and water.…”

Environmental risk factors of systemic sclerosis

“…Nevertheless, in this group of exposed patients, because asbestos was concurrent with crystalline silica exposure (contaminated vermiculite), it is difficult to assess the role of each material separately. Moreover, based on examination of US death certificates of SSc patients (n=5642), Gold et al [40] have also observed an Table 1 Occupations associated with exposure to crystalline silica -Work of drilling, demolition, extraction, and transport of ores or rocks containing free silica -Crushing, grinding, sifting, and handling carried-out dry ores or rocks containing free silica -Cutting and polishing of rocks containing free silica -Manufacture and handling of grittings, scouring powders, or other products containing free silica -Work of sanding and dry sawing of materials containing free silica -Work in the coal mines -Extraction, splitting, cutting, smoothing, and polishing of slates -Use of crushed slate dust in rubber factory or in the preparation of cement or sinter -Extraction, crushing, and conditioning of talc -Use of talc like lubricant or like charges in paper sizing, certain paintings, preparation of cosmetic powders, and mixtures of rubbers -Manufacture of carborundum, glass, porcelain, earthenware, and other products such as ceramics and refractory products -Work of foundry exposing to dust of sand, stripping, trimming, and desanding -Work of grinding, polishing, and dry grinding by means of grinding wheels containing free silica -Work of scouring or polishing to the sand blast -Building work and demolition exposing to the inhalation of dust containing free silica association between occupational asbestos exposure and SSc (OR 1.2, 95 % CI 1.1-1.3).…”

414 Induction of il-17 production from human peripheral blood cd4+ cells by asbestos exposure

“…It appears that Th17 cells play a complex and controversial role in tumor immunity. A study of the effects of asbestos on Th17 cells in a murine model using erionite, which has similar chemical and physical properties to asbestos, demonstrated induced production of IL-17 (28). Similarly, a study utilizing amphibole asbestos, but not chrysotile asbestos, demonstrated induced production of IL-17 in a murine model (29).…”