title: Platinum-induced autoantibodies target nucleoplasmic antigens related to active transcription.
abstract: Research on autoimmune diseases has revealed that autoimmunity can be induced by heavy metals such as mercury and gold. Following the introduction of platinum-containing catalytic converters in automobiles, the emission of platinum compounds constitutes an abundant environmental pollutant, however, potential immunological hazards resulting from platinum-containing emissions were not yet examined. In our previous studies on molecular mechanisms of heavy metal-induced autoimmunity, we showed a platinum-dependent subcellular redistribution of the autoantigen fibrillarin from the nucleolus to the nucleoplasm. Since H-2s mice constitute a valuable model to study the role of heavy metals in the development of systemic autoimmunity, we treated susceptible B10.S mice with hexachloroplatinate (Na2PtCl6, Pt4+) to examine whether platinum induces the production of autoantibodies. The present study shows for the first time that chronic administration of Pt4+ generated an autoimmune response in mice which targets distinct nucleoplasmic antigens. Dual-labeling revealed substantial colocalization of these nucleoplasmic autoantigens with (i) nascent RNA, (ii) the active, phosphorylated form of RNA polymerase II, and partial overlap with (iii) acetylated histone 4 protein, and (iv) 20S proteasomes in dendritic cells isolated from platinum-treated mice. The results suggest that platinum elicits antibodies against antigens associated with active sites of transcription which may be subject to proteasomal processing during heavy metal-induced autoimmunity.
authors.affiliation: Junior Research Group of Molecular Cell Biology, Institut für Umweltmedizinische Forschung, Heinrich-Heine-University, Düsseldorf, Germany. chenmin@uni-duesseldorf.de
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Hemmerich
authors.forename: Anna
authors.initials: A
authors.lastname: von Mikecz
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology*; D034961:Antigens, Nuclear / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000235:genetics; D002460:Cell Line; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000276:immunology / Q000633:toxicity*; D003546:Cysteine Endopeptidases / Q000648:ultrastructure; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D005260:Female; D006657:Histones / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D018613:Microscopy, Confocal; D009097:Multienzyme Complexes / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex; D012313:RNA / Q000276:immunology; D012319:RNA Polymerase II / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D000974:Antibodies, Antinuclear; D034961:Antigens, Nuclear; D006657:Histones; D009097:Multienzyme Complexes; D012313:RNA; D012319:RNA Polymerase II; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D002945:Cisplatin; C038762:disodium hexachloroplatinate