Hostname: page-component-77c89778f8-fv566 Total loading time: 0 Render date: 2024-07-16T16:17:54.709Z Has data issue: false hasContentIssue false

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
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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

References

REFERENCES

Aebi, H. E. (1983). Catalase. Methods in Enzymatic Analysis 3, 273286.Google Scholar
Babu, U. & Failla, M. L. (1990). Respiratory burst and candidacidal activity of peritoneal macrophages are impaired in copper deficiency. Journal of Nutrition 120, 16921699.CrossRefGoogle Scholar
Bode, A. M., Miller, L. A., Faber, J. & Saari, J. T. (1992). Mitochondria1 respiration in heart, liver and kidney of copper-deficient rats. Journal of Nutritional Biochemistry 3, 668672.CrossRefGoogle Scholar
Boobis, A. R., Fawthorp, D. J. & Davies, D. S. (1989). Mechanisms of cell death. Trends in Physiological Sciences 10, 175180.Google ScholarPubMed
Collins, S. J., Gallo, R. C. & Gallagher, R. E. (1977). Continuous growth and differentiation of human myeloid cells in suspension culture. Nature 270, 347350.Google Scholar
Cooperstein, S. J. & Lazarow, A. (1951). A microspectrophotometric method for the determination of cytochrome oxidase. Journal of Biological Chemistry 189, 6656707.CrossRefGoogle ScholarPubMed
Cory, V. G. (1983). Role of ribonucleotide reductase in cell division. Pharmacological Therapeutics 21, 265276.CrossRefGoogle ScholarPubMed
Epstein, M. A. & Barr, Y. M. (1964). Culture in vitro of Burkitt's malignant lymphoma. Lancet i, 253255.Google Scholar
Harris, E. D. (1983). Copper in human and animal health. In Trace Elements in Health: A Review of Current Issues, pp. 4473 [Rose, J., editor ]. London: Butterworths.CrossRefGoogle Scholar
Jones, D. G. & Suttle, N. F. (1981). Some effects of copper deficiency on leucocyte functionin sheep and cattle. Research in Veterinary Science 31, 151156.Google Scholar
Lukasewycz, O. A., Prohaska, J. R., Meyer, S. G., Schmidtke, J. R., Hatfield, S. M. & Marder, P. (1985). Alterations in lymphocyte sub-populations in copper-deficient mice. Infection and Immunity 48, 644647.Google Scholar
Martin, S. J., Mazdai, G., Strain, J. J., Cotter, T. G. & Hannigan, B. M. (1991). Programmed cell death (apoptosis) in lymphoid and myeloid cell lines during zinc deficiency. Clinical Experimental Immunology 83, 338343.Google Scholar
Minowada, J., Ohnuma, T. & Moore, G. E. (1972). Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. Journal of the National Cancer Institute 49, 891899.Google Scholar
Orrenius, S., McConkey, D. J., Bellomo, G. & Nicotera, P. (1989). Role of Ca2+ in toxic cell killing. Trends in Physiological Sciences 10, 281285.CrossRefGoogle ScholarPubMed
Paglia, D. E. & Valentine, W. N. (1967). Studies on the quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. Journal of Laboratory and Clinical Medicine 70, 158169.Google ScholarPubMed
Podczasy, J. J. & Wei, R. (1988). Reduction of iodonitrotetrazolium violet by superoxide radicals. Biochemicaland Biophysical Research Communications 150, 12941301.CrossRefGoogle ScholarPubMed
Prohaska, J. R., Downing, S. W. & Lukasewycz, O. A. (1983). Chronic dietary copper deficiency alters biochemical and morphological properties of mouse lymphoid tissue. Journal of Nutrition 113, 15831590.Google Scholar
Roath, S., Newell, D., Polliack, A., Alexander, E. & Lin, P. S. (1978). Scanning electron microscopy and the surface morphology of human lymphocytes. Nature 273, 1518.CrossRefGoogle ScholarPubMed
Schanne, F. A. X., Kane, A. B., Young, E. E. & Faber, J. L. (1979). Calcium dependence of toxic cell death. A final common pathway. Science 206, 700702.CrossRefGoogle ScholarPubMed
Stabel, J. R. & Spears, J. W. (1989). Effect of copper on immune function and disease resistance. Advances in Experimental Medicine and Biology 258, 243252.Google Scholar
Strain, J. J. (1994). Putative role of dietary trace elements in coronary heart disease and cancer. British Journal of Biomedical Science 51, 241251.Google ScholarPubMed
Underwood, E. J. (1977). Trace Elements in Human and Animal Nutrition, 5th ed. New York: Academic Press.Google Scholar
Wlostowski, T. (1993). Involvement of metallothionein and copper in cell proliferation. Biometals 6, 7176.Google Scholar