Accumulation of metallothionein and its multiple forms by zinc, cadmium and dexamethasone in human peripheral T 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 concentrations, 125 microM for Zn and 10 microM 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 all 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 compared to Zn. Zn and dex in combination showed the same accumulation rate as Zn alone. If the inductors were used in lower concentrations than optimal, reduced accumulation rates occurred, particularly during the first part of the exposure period. No MT was found for concentrations below 5 microM Zn, 1 microM Cd or 0.5 microM dex. The constitutive levels of MT (mean +/- S.E.M.) were 0.11 +/- 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 microM 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 microM Zn for 2 days, removal of the metal caused constitutive MT levels to be reestablished in 5 days. Five different MT forms, all capable of Cd complexation, were demonstrated in these cells. These forms had kinetically different behaviour during Zn exposure among the cell types, and the response to Cd was different from the Zn response. The results indicate metals to be closely controlled in MNC and emphasize a role for multiple MT forms in the process of regulation.
Mesna
O J
OJ
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
Steffensen
I L
IL
Hjertholm
H
H
Andersen
R A
RA
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002104:Cadmium / Q000097:blood / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000097:blood*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D006454:Hemoglobins; D002104:Cadmium; D003907:Dexamethasone; D008668:Metallothionein; D015032:Zinc