Total cell-associated Zn⁺⁺ and Cu⁺⁺ and proliferative responsiveness of peripheral blood mononuclear cells from patients on chronic hemodialysis

We investigated total copper (Cu⁺⁺) and zinc (Zn⁺⁺) content in plasma and peripheral blood mononuclear cells (PBMC) and its impact on proliferative ability of the latter in patients on chronic hemodialysis versus age- and sex-matched healthy volunteers. Plasma levels of Cu⁺⁺ and Zn⁺⁺ were significantly lower in dialysis patients compared with the control group (83.6 ± 7.29 v 95.1 ± 9.63 μg/dL, P < .03 for Cu⁺⁺; 71.1 ± 7.64 v 89.7 ± 12.55 μg/dL, P < .005 for Zn⁺⁺). Basal total PBMC-associated Cu⁺⁺ content was significantly higher in uremic patients (19.3 ± 3.59 v 14.6 ± 2.72 μmol/mg protein, P < .005). Basal PBMC-associated Zn⁺⁺ concentration was also significantly elevated in hemodialysis patients compared with their healthy counterparts (23.9 ± 5.64 v 10.5 ± 2.64 μmol/mg protein, P < .005). In addition, we incubated PBMC of the uremic patients versus healthy control PBMC in a Zn⁺⁺-free versus Zn⁺⁺-enriched medium. After a 72-hour incubation, total cell-associated Zn⁺⁺ of both normal and uremic cell populations increased significantly compared with the respective baselines (34.6 ± 22.49 v 4.3 ± 1.42 and 20.3 ± 10.71 v 5.8 ± 2.22 μmol/mg protein, respectively). However, no statistically significant differences was evident between the 2 groups (34.6 ± 22.49 v 20 ± 10.7 μmol/mg protein). Total cell Zn⁺⁺ content, on the other hand, was significantly increased in uremic PBMC after 72 hours of incubation in Zn⁺⁺-enriched medium compared with the control group (63.3 ± 26.12 v 18.6 ± 13.42 μmol/mg protein, P < .005). A significant increase in PBMC proliferation evaluated by ³H-thymidine incorporation was evident in the Zn⁺⁺-enriched culture (35,559 ± 4,136 counts per minute [CPM] v 20,497 ± 7,263 CPM, P < .005). Cu⁺⁺ enrichment of the medium, while resulting in a modest elevation of cell-associated Cu⁺⁺, did not produce such a proliferation effect.