Libby amphibole-induced mesothelial cell autoantibodies promote collagen deposition in mice.
Libby amphibole (LA) causes a unique progressive lamellar pleural fibrosis (LPF) that is associated with pulmonary function decline. Pleural fibrosis among the LA-exposed population of Libby, MT, has been associated with the production of anti-mesothelial cell autoantibodies (MCAA), which induce collagen production from cultured human mesothelial cells. We hypothesized that the progressive nature of LPF could be at least partially attributed to an autoimmune process and sought to demonstrate that LA-induced MCAA trigger collagen deposition in vivo. C57BL/6 mice were exposed to LA for 7 mo, and serum was tested for MCAA by cell-based ELISA on primary mouse mesothelial cells. When treated in vitro with serum from mice exposed to LA, mesothelial cells upregulated collagen matrix production. This effect was lost when the serum was cleared of IgG using protein G beads, implicating IgG autoantibodies. Using the peritoneal cavity as a surrogate for the pleural cavity, groups of naïve (non-asbestos-exposed) mice were injected intraperitoneally with 1) control serum, 2) one dose of serum from LA-exposed mice (LA serum), 3) two doses of LA serum, or 4) two doses of LA serum cleared of IgG. After 1 mo, analysis of collagen in peritoneal walls using two-photon confocal microscopy (SHG analysis) and a hydroxyproline assay demonstrated significant increases in collagen by LA serum but not control or cleared serum. These data support the hypothesis that MCAA in LA-exposed mice induce fibrotic responses in vivo, demonstrating that an autoimmune component may be contributing to the progressive pleural fibrosis seen in LA-exposed patients.
Department of Biological Sciences, Idaho State University, Pocatello, Idaho; and.
John
J
Gilmer
Department of Natural Sciences, Mars Hill University, Mars Hill, North Carolina.
Kinta
K
Serve
Department of Biological Sciences, Idaho State University, Pocatello, Idaho; and.
Chad
C
Davis
Department of Biological Sciences, Idaho State University, Pocatello, Idaho; and.
Marti
M
Anthony
Department of Biological Sciences, Idaho State University, Pocatello, Idaho; and.
Robert
R
Hanson
Department of Biological Sciences, Idaho State University, Pocatello, Idaho; and.
Tanner
T
Harding
Department of Biological Sciences, Idaho State University, Pocatello, Idaho; and pfaujean@isu.edu.
Jean C
JC
Pfau
D000818:Animals; D017636:Asbestos, Amphibole / Q000633:toxicity*; D001195:Asbestosis / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology*; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D024022:Fibrillar Collagens / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008810:Mice, Inbred C57BL; D010995:Pleural Diseases / Q000276:immunology / Q000378:metabolism; D061251:Primary Cell Culture
D017636:Asbestos, Amphibole; D001323:Autoantibodies; D024022:Fibrillar Collagens
amphibole asbestos; autoimmunity; pleural/peritoneal fibrosis