title: Exposure to inorganic mercury in vivo attenuates extrinsic apoptotic signaling in Staphylococcal aureus enterotoxin B stimulated T-cells.
abstract: The heavy metal mercury (Hg) is known to have immunomodulatory properties affecting lymphocyte signal transduction, death receptor signaling and autoimmunity. In this study we tested the hypothesis that Hg exposure would attenuate T-cell activation and caspase 8 and 3 activity in response to antigenic stimuli. To test this hypothesis, BALB/cJ mice were exposed to 10 mg/l mercuric chloride (HgCl(2)) in their drinking water for 2 weeks followed by injection with 20 microg of the Staphylococcal aureus enterotoxin B (SEB) superantigen. Eighteen hours after SEB challenge, there was a statistically significant reduction in caspase 8 and caspase 3 enzyme activity in the SEB reactive Vbeta8+ T-cells. The attenuated caspase activity in Hg-exposed mice persisted for 48 h after exposure. Moreover, activation of caspase 8 and caspase 3 was reduced by more than 60% in CD95 deficient MRL/MpJ-Fas(lpr) mice demonstrating that caspase 8 and 3 activation in response to SEB is CD95 dependent. In addition to the effects of Hg on caspase activity, expression of the T-cell activation marker CD69 was also attenuated in SEB reactive Vbeta8 T-cells in Hg-exposed mice. Moreover, CD69 expression in MRL/MpJ-Fas(lpr) mice was also reduced. Taken together the caspase and CD69 data support a role for CD95 in promoting a proapoptotic and activated state in SEB responsive T-lymphocytes and this state is attenuated by the autoimmune potentiating environmental agent mercury.
authors.affiliation: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Laiosa
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Eckles
authors.forename: Margaret
authors.initials: M
authors.lastname: Langdon
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Rosenspire
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McCabe
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053181:Caspase 8 / Q000187:drug effects / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D037181:Lectins, C-Type; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D019014:fas Receptor / Q000187:drug effects* / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D053148:Caspase 3; D053181:Caspase 8; D004768:Enterotoxins; D037181:Lectins, C-Type; D008627:Mercuric Chloride; D018089:Superantigens; D019014:fas Receptor; D000099192:CD69 Antigens; C031818:enterotoxin B, staphylococcal