Inhibition of lectin-induced lymphocyte activation by 2-cyclohexene-1-one: decreased intracellular glutathione inhibits an early event in the activation sequence
Fischman, C.M.; Udey, M.C.; Kurtz, M.; Wedner, H.J.
Journal of Immunology 127(6): 2257-2262
1981
ISSN/ISBN: 0022-1767 PMID: 6975313 Document Number: 182157
The importance of normal intracellular glutathione (GSH) levels in the activation of human peripheral blood lymphocytes (PBL) by mitogenic lectins was explored using 2-cyclohexen-1-one (2-CHX-1), an agent that selectively decreases the levels of intracellular GSH. PBL incubated with mitogenic lectins and graded doses of 2-CHX-1 showed a dose-dependent inhibition of activation assayed by [3H]-thymidine uptake and percentage of blast transformation. 2-CHX-1 (2.5 .times. 10-5 M), a concentration that decreases GSH levels to < 20% of control, caused an 80-90% suppression of both [3H]-thymidine uptake and blast transformation; lower concentrations were less effective. Time course studies showed that 2-CHX-1 wa was maximally effective only if added during the first 4 h of culture. At the concentrations used, 2-CHX-1 was not cytotoxic to lectin-stimulated or unstimulated PBL and did not interfere with mitogen-lymphocyte interaction. Adequate levels of glutathione appear to be necessary for lymphocyte activation and the glutathione requirement is exerted in the early activation sequence.