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The effects of copper deficiency on human lymphoid and myeloid cells: an in vitro model

Published online by Cambridge University Press:  09 March 2007

K. K. Tong
Affiliation:
Cancer and Ageing Research Group, University of Ulster, Coleraine BT52 ISA
Bernadette M. Hannigan
Affiliation:
Cancer and Ageing Research Group, University of Ulster, Coleraine BT52 ISA
George Mckerr
Affiliation:
Cancer and Ageing Research Group, University of Ulster, Coleraine BT52 ISA
John J. Strain
Affiliation:
Human Nutrition Research Group, University of Ulster, Coleraine BT52 ISA
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Abstract

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Cu has long been known to influence immune responses. An in vitro model system was established in which human myeloid(HL-60), B-lymphoid (Raji) and T-lymphoid (Molt-3) cell lines could be grown in culture media of varying Cu levels. Initially Cu was removed from the medium by dialysisof fetal calf serum against a metal-ion chelator, minor depletion of other trace metals being obviated by repletion with appropriate metal salts. The growth rate of HL-60 was significantly (P<0·05) inhibited by 72 h Cu depletion. Molt-3 cells required a longer period, up to 144 h, in Cudepleted medium before growth was impaired. Raji-cell growth was not affected. These results confirmed clinical observations that T-cell functions were more sensitive to Cu deprivation than B cells. Analysis of intracellular metal levels in Molt-3 cells showed that Cu levels had been significantly lowered (P <0·05) although Ca2+ levels were raised. Intracellular activity of the antioxidant enzyme superoxide dismutase (EC 1. 15. 1. 1) was significantly impaired (P<0·05) in Molt-3 cells grown in Cudepleted medium. Activity of the mitochondria1 enzyme cytochrome c oxidase (EC 1. 9. 3. 1) was also significantly impaired (P <0·05) by Cu depletion. Each of these findings indicates an increase in the potential for cellular damage by reduced antioxidant activity, impairment of normal mitochondrial activity and excessive Ca2+influx. A major consequence of the type of damage occurring under these circumstances is membrane disruption. This was confirmed by scanning electron microscopy of Molt-3 cells grown under varying Cu levels.

Type
Copper deficiency and immunity
Copyright
Copyright © The Nutrition Society 1996

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