Suppression of lymphocyte proliferation by copper-albumin chelates.
The copper-albumin chelate (Cu2+-Alb), at concentrations less than 100 micrograms/ml, has potent noncytolytic antiproliferative activity for murine splenocytes stimulated by phytohemagglutinin-M, lipopolysaccharide (Escherichia coli 055:B5), or allogeneic cells and for phytohemagglutinin-M-stimulated human leukocytes. Inhibitory effects on the incorporation of [3H]leucine into trichloroacetic acid-precipitable protein is observed only at concentrations of Cu2+-Alb above 1 mg/ml. Only albumins with a histidine residue at position number 3 (rabbit, human, bovine) which bind one copper molecule at a high affinity site are capable of eliciting Cu2+-dependent suppression. Canine albumin, which has a tyrosine residue at position 3 and does not bind Cu2+, is nonsuppressive . Copper-albumin is suppressive in both the G1 and S phases of the cell cycle, thus clearly differentiating its suppressive activity from that of normal human plasma. It is not clear, however, if the Cu2+-Alb chelate is the active suppressive species or whether albumin is more efficient than other Cu2+ chelates in donating Cu2+ to another suppressive molecule. The biological significance of Cu2+-Alb-induced suppression is unknown. Although several possibilities are discussed, the potential to generate "artifactual" suppression by the formation of Cu2+-Alb chelates as a result of protein isolation procedures using Cu2+-contaminated reagents is considered to be an important potential problem.
D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D003078:Colchicine / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D019327:Copper Sulfate; D004261:DNA Replication / Q000187:drug effects; D004285:Dogs; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D010835:Phytohemagglutinins / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D000418:Albumins; D002614:Chelating Agents; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D012710:Serum Albumin, Bovine; D003300:Copper; D019327:Copper Sulfate; D003078:Colchicine; D013936:Thymidine