Fe- and Zn-induced inhibition of Cd uptake in human lung cell lines: Speciation studies with H441 and A549 cells

Cadmium transport was studied in human lung cell lines A549 and H441 as a function of inorganic metal speciation. A 2-fold higher equilibrium accumulation was obtained in the A549 cells, but a specific system of transport of high affinity and low capacity was characterized in both these cells. Exposure conditions optimizing [Cd2+] increased Cd uptake, but CdCln2-n species are also taken up. Studies on Cd-Ca reciprocal inhibition do not support a role for Ca pathways in Cd uptake. Nramp2 and Zip8 mRNAs were detected in both cell lines. Fe inhibited Cd uptake in the nitrate medium with an apparent at pH 5.5. NRAMP2 may contribute to Cd uptake but a major role is precluded since the overall process of accumulation was inhibited by acidic conditions. Zn and Mn inhibited Cd uptake with the following observations: (1) Similar apparent Ki values for Zn-induced inhibition in the chloride and nitrate media. (2) Whatever the medium, a higher Mn-induced inhibition at pH 5.5 compared to pH 7.4, with much lower Ki values under acidic conditions. (3) Elimination of the stimulatory effect of HCO3- by Zn but not by Mn. Zn may inhibit a ZIP8-mediated Cd uptake, whereas the Mn-sensitive component of uptake would be related to other transport processes.

► A 2.5-fold higher level of accumulation at equilibrium in A549 cells compared to H441 cells. ► Presence of specific uptake of Ca but these pathways are not involved in Cd uptake. ► H441 and A549 cells express Nramp2 and Zip8 mRNA. ► NRAMP contribution to the overall process of accumulation would not be predominant. ► Zn, but not Mn, may inhibit a ZIP8-mediated Cd uptake.