Dose-dependent apoptosis induced by low concentrations of methylmercury in murine splenic Fas+ T cell subsets.
Methylmercury chloride (MeHgCl) is known to induce cellular and humoral immunodeficiencies in mice. In this study, the involvement of lymphoid subset disorders due to low concentrations of methylmercury (0.001-1.0 microM) has been examined. Cytofluorometric analysis of splenic cells exposed in vitro to low concentrations of MeHgCl for 48 h revealed two distinct populations: the first expressed a typical lymphoid forward light scatter (FSC)/side light scatter (SSC) pattern (R1 region), and the second was characterized by a lower FSC and a higher SSC (R2 region). A dose-dependent shift of cells from R1 region toward R2 region was observed in splenic cells treated with MeHgCl. The apoptotic state of cells in the R2 region was confirmed by the TdT-mediated dUTP nick end labeling (TUNEL) assay. Analysis of DNA content in splenic lymphoid cells showed that low concentrations of MeHgCl increased both hypoploid cells and cells in G0-G1/S phase, both in the R1 and R2 regions. However, the numbers of cells in G0-G1/S and G2/M phases were decreased, but hypoploid cells increased in both regions due to exposure to 1 microM MeHgCl. MeHgCl-induced apoptosis disappeared when splenic cells were pretreated with anti-Fas antibodies, indicating that Fas expressing cells were the target cells for MeHgCl-mediated apoptosis. Furthermore, T cells from the V beta 8 family were found to be more sensitive to apoptosis induced by low concentrations of MeHgCl. Taken together, these results suggest that MeHgCl at low concentrations mediates the development of apoptosis in peripheral T cell via the Fas/FasL pathway.
Pheng
S
S
Département de Médecine du Travail et d'Hygiène du Milieu, Faculté de Médecine, Université de Montréal, Québec, Montréal, Canada.
Chakrabarti
S
S
Lamontagne
L
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000378:metabolism; D008767:Methylmercury Compounds / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D008767:Methylmercury Compounds; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor; C004925:methylmercuric chloride