Dose-dependent apoptosis induced by low concentrations of methylmercury inmurine splenic Fas plus T cell subsets

Methylmercury chloride (MeHgCl) is known to induce cellular and humoral imm unodeficiencies in mice. In this study, the involvement of lymphoid subset disorders due to low concentrations of methylmercury (0.001-1.0 mu M) has b een examined. Cytofluorometric analysis of splenic cells exposed in vitro t o low concentrations of MeHgCl for 48 h revealed two distinct populations: the first expressed a typical lymphoid forward light scatter (FSC)/side lig ht 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 fr om R1 region toward R2 region was observed in splenic cells treated with Me HgCl. The apoptotic state of cells in the R2 region was confirmed by the Td T-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 regi ons. However, the numbers of cells in G0-G1/S and G2/M phases were decrease d, but hypoploid cells increased in both regions due to exposure to 1 mu M MeHgCl. MeHgCl-induced apoptosis disappeared when splenic cells were pretre ated with anti-Fas antibodies, indicating that Fas expressing cells were th e 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 lo w concentrations of MeHgCl. Taken together, these results suggest that MeHg Cl at low concentrations mediates the development of apoptosis in periphera l T cell via the Fas/FasL pathway. (C) 2000 Elsevier Science Ireland Ltd. A ll rights reserved.