Effects of cadmium on lymphocyte activation.
The effects of cadmium (Cd) on phytohemoagglutinin or phorbol myristate acetate-induced lymphocyte activation were investigated and a dose-dependent inhibition of cell proliferation was found. Kinetic studies revealed that the Cd-sensitive step is an early event of T cell stimulation. Failure of IL2 secretion and reduction of IL2 receptor expression in the Cd-treated cells are also reported. Regardless of which mechanism is responsible for Cd effects, our studies show that the inhibition of lymphocyte activation is associated with reduced [3H]phorbol dibutyrate binding to Ca2+-phospholipid-dependent protein kinase and altered breakdown of phosphatidylinositols. Thus, Cd interferes with two biochemical events which play a critical role in lymphocyte signal transduction and activation.
Grazia Cifone
M
M
Dipartimento di Medicine Sperimentale, Universitá degli Studi di L'Aquila, Italy.
Alesse
E
E
Procopio
A
A
Paolini
R
R
Morrone
S
S
Di Eugenio
R
R
Santoni
G
G
Santoni
A
A
D000328:Adult; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride; D002106:Cadmium Radioisotopes; D002118:Calcium / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002106:Cadmium Radioisotopes; D007378:Interleukins; D010716:Phosphatidylinositols; D010743:Phospholipids; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D002104:Cadmium; D015240:Phorbol 12,13-Dibutyrate; D011494:Protein Kinases; D019256:Cadmium Chloride; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium