Cellular binding and/or uptake of nickel(II) ions.
L-Histidine (L-His) and human serum albumin (HSA) at physiological concentrations, like the exogenous ligands D-penicillamine (D-PEN) and EDTA, are shown to inhibit the uptake of physiological levels of Ni2+ by B-lymphoblasts of human origin, human erythrocytes and rabbit alveolar macrophages. Evidence is also presented that illustrates the ability of these ligands to sequester Ni2+ from cells preloaded with this ion. The experimental observations are interpreted to indicate that serum concentrations of HSA and amino acids (especially L-His) exert a controlling influence on the cellular accumulation of Ni2+ in vitro, and further suggest the necessity to standardize the concentrations of these and related constituents in cell-culture media for meaningful comparisons of cellular uptake and toxicity of Ni2+ and other metal ions. Cells were lysed and the fractional distribution of 63Ni2+ in the lysate and residual pellet were assessed. About 60% of the radiolabel occurred in the pellet and 40% in the lysate for B-lymphoblasts, compared to 70 and 30% respectively for the alveolar macrophages. Diethyldithiocarbamate (DDC), unlike the other complexing agents, enhanced the cellular uptake of Ni2+ and prevented its removal from loaded cells. DDC also induced a transfer of the 63Ni2+ from the lysate to the residual pellet, suggesting that it promotes the deposition of Ni2+ in the lipid-rich components of cells (tissues). It is concluded that cellular association of Ni2+ is favoured by ligands forming lipophilic complexes, and extracellular localization by those giving hydrophilic complex compounds. The relevance of these contrasting roles in nickel detoxification by endogenous ligands and chelating drugs is discussed.
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002413:Cations, Divalent; D002614:Chelating Agents / Q000494:pharmacology*; D003470:Culture Media; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008264:Macrophages / Q000378:metabolism; D009532:Nickel / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology; D011817:Rabbits
D002413:Cations, Divalent; D002614:Chelating Agents; D003470:Culture Media; D008024:Ligands; D009532:Nickel