title: Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages.
abstract: Asbestos exposure is associated with increased autoimmune responses in humans. For example, in Libby, MT where significant asbestos exposure has occurred due to an asbestos-contaminated vermiculite mine near the community, residents have developed increased autoimmune responses compared to an unexposed population. However, the exact mechanism by which Libby amphibole asbestos generates autoimmune responses is unclear. A murine model of amphibole asbestos-induced autoimmunity was recently established, and one of the targets of the autoantibodies (AAs) was the SSA/Ro52 autoantigen. The purpose of this study was to determine whether the SSA/Ro52 autoantigen is exposed at the surface of cells as a result of asbestos exposure as a possible mechanism leading to antigenicity. Our results indicate that Libby asbestos induces apoptosis in murine macrophages as determined by phosphatidylserine exposure, cleavage of poly(ADP-ribose) polymerase and morphological changes such as nuclear condensation. Moreover, asbestos-induced apoptosis results in the formation of apoptotic cell surface blebs enriched in SSA/Ro52 as determined by confocal microscopy. Most importantly, apoptotic cell surface blebs are recognized by AAs from mice exposed to amphibole asbestos suggesting that these cell surface structures may be antigenic when presented in a pro-inflammatory context. This study supports the hypothesis that the induction of apoptosis plays a key role in environmentally induced autoimmunity through cell surface exposure of a known autoantigen.
authors.affiliation: Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA. dblake@jhsph.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Blake
authors.forename: Scott A
authors.initials: SA
authors.lastname: Wetzel
authors.forename: Jean C
authors.initials: JC
authors.lastname: Pfau
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D017636:Asbestos, Amphibole / Q000633:toxicity*; D001323:Autoantibodies / Q000378:metabolism*; D015551:Autoimmunity / Q000187:drug effects* / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D022081:Cell Surface Extensions / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D018613:Microscopy, Confocal; D012261:Ribonucleoproteins / Q000378:metabolism*; D000099207:SS-A Antigen
chemical_list: D017636:Asbestos, Amphibole; D001323:Autoantibodies; D015415:Biomarkers; D012261:Ribonucleoproteins; D000099207:SS-A Antigen