ACCUMULATION OF METALLOTHIONEIN AND ITS MULTIPLE FORMS BY ZINC, CADMIUM AND DEXAMETHASONE IN HUMAN PERIPHERAL T-LYMPHOCYTES AND B-LYMPHOCYTES AND MONOCYTES

Metallothionein (MT) is produced at high rates in isolated monocytes, and T and B lymphocytes during induction in vitro. At optimal concentr ations, 125 mu M for Zn and 10 mu M for Cd and dexamethasone (dex), MT was demonstrated after only 2 h in some cases, and in all cell types substantial levels were measured after 1 day of exposure to ail three inductors. With Cd, lower amounts of MT were found, but maximum levels were reached faster than with Zn. The same result was found for dex c ompared to Zn. Zn and dex in combination showed the same accumulation rate as Zn alone. If the inductors were used in lower concentrations t han optimal, reduced accumulation rates occurred, particularly during the first part of the exposure period. No MT was found for concentrati ons below 5 mu M Zn, 1 mu M Cd or 0.5 mu M dex. The constitutive level s of MT (mean +/- S.E.M.) were O.11 +/- 0.05, 0.54 +/- 0.3, 0.06 +/- 0 .05 and 0.15 +/- 0.08 nmol Cd bound/5 x 10(6) unseparated mononuclear cells (MNC), monocytes, T lymphocytes and B lymphocytes, respectively. Monocytes accumulated 19 times and B lymphocytes 6 times more MT than T lymphocytes after 2 days of exposure to 125 mu M Zn. Despite these differences in accumulated amounts of MT, the fold accumulation values were rather similar between the cell types, reflecting corresponding variations in background MT levels. After exposure of unseparated MNC to 125 mu M Zn for 2 days, removal of the metal caused constitutive MT levels to be reestablished in 5 days. Five different MT forms, all ca pable of Cd complexation, were demonstrated in these cells, These form s had kinetically different behaviour during Zn exposure among the cel l types, and the response to Cd was different from the Zn response. Th e results indicate metals to be closely controlled in MNC and emphasiz e a role for multiple MT forms in the process of regulation.