Journal
TOXICOLOGY
Volume 246, Issue 2-3, Pages 172-179Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2008.01.008
Keywords
asbestos; macrophage; apoptosis; autoimmunity; immunotoxicology
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Funding
- NCRR NIH HHS [P20 RR017670-03, P20 RR017670] Funding Source: Medline
- NIEHS NIH HHS [R21 ES012956, R21 ES012956-02] Funding Source: Medline
- NIGMS NIH HHS [P30 GM103338] Funding Source: Medline
- PHS HHS [P20 NCRR017670] Funding Source: Medline
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Asbestos exposure is associated with increased autoimmune responses in humans. For example, in Libby, NIT 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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