Effects of Cd2+ upon Ca2+ fluxes and proliferation in concanavalin A-stimulated lymphocytes.
The mitogenic response of human peripheral blood lymphocytes to the lectin concanavalin A (conA) is inhibited by micromolar concentrations of CdCl2. This inhibition is partially relieved by an increase in the external Ca2+ concentration (from 0.6 to 2.2 mM). The initial rate of conA-induced 45Ca2+ influx is unaltered by CdCl2, although the level of 45Ca2+ accumulation increases. The basal rate of 45Ca2+ entry is not measurably disturbed by CdCl2 (100 microM). The steady-state efflux of 45Ca2+ and the calmodulin-activated (Ca2+ + Mg2+)-ATPase activity of erythrocyte ghosts are inhibited by CdCl2 (10 microM). Thus, the mechanism behind the Cd2+-induced suppression of the mitogenic response to conA is not due to alteration of mitogen-stimulated Ca2+ influx. We suggest that Cd2+ competes with Ca2+ for intracellular Ca2+-binding molecules, such as calmodulin, essential for the induction of cell proliferation.
Scott
I G
IG
Wolff
C H
CH
Akerman
K E
KE
Andersson
L C
LC
D001693:Biological Transport, Active / Q000187:drug effects; D017301:Ca(2+) Mg(2+)-ATPase; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000097:blood; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000201:enzymology; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D002104:Cadmium; D003208:Concanavalin A; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D019256:Cadmium Chloride; D002118:Calcium