This paper is only available as a PDF. To read, Please Download here.
Abstract
Zinc deficiency alters lymphocyte and monocyte function in man and animals. A patient
with isolated zinc deficiency was found to have lymphopenia (420 lymphocytes/μl),
depressed T-cell mitogen response (48% of normal control), increased numbers of circulating
T-suppressor cells (OKT8 reactive cells) and decreased circulating T-helper cells
(OKT4 reactive cells). Activity of the patient's natural killer (NK) cells was 1 lytic
unit/106 cells (normal 10 to 40), and monocyte cytotoxicity (MC) was four times that of normal
controls. Zinc repletion in vivo improved the peripheral lymphocyte count, corrected
the abnormal OKT8-to-OKT4 ratio, normalized T-cell response to mitogen, improved NK
function, and lowered MC to control values. A divalent cation chelator, 1,10-orthophenanthroline
(OP), was used to simulate zinc deficiency in vitro. T-cells exposed to OP are nonresponsive
to mitogen unless zinc is added. NK function of lymphocytes from normal donors exposed
to OP was depressed in a time- and dose-dependent manner. NK activity of peripheral
blood lymphocytes (PBL) from 12 normal donors exposed to 50 μM OP for 16 hr was 10.3
± 7 lytic units/106 cells (mean ± S.E.M.) vs. 32.6 ± 14 for cells incubated in medium alone. When monocytes
were exposed for 16 hr to 50 μM OP, however, MC significantly increased to a range
two to five times that of control. OP-induced alterations of lymphocyte and monocyte
function was reversed by the addition of 50 μM zinc but not calcium or magnesium.
Since NK activity and MC are thought to be important in host tumor immunity, alterations
in zinc metabolism may have important implications for human tumor immune surveillance
mechanisms.
Abbreviations:
natural killer cell ((NK)), sheep erythrocyte rosetting ((ER)), monocyte cytotoxicity ((MC)), 110-orthophenanthroline ((OP)), phytohemagglutinin ((PHA)), RPMI with 10% fetal calf serum ((RPMI-FCS)), RPMI with 10% human Type AB serum ((RPMI-AB)), RPMI with 20% autologous serum ((RPMI-AS)), RPMI-AB with trypticase soy broth ((RPMI-ABTryp)), peripheral blood lymphocytes ((PBL)), phosphate-buffered saline ((PBS)), lytic unit(s) ((LU)), ethylenediaminetetraacetate ((EDTA))To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Translational ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Nutrition and immunity.J Clin Immunol. 1981; 1: 3
- 1,10-Phenanthroline inhibition of lymphoblast cell cycle.Cancer Res. 1977; 37: 2050
- Effect of zinc on cells and biomembranes.Med Clin North Am. 1976; 60: 799
- Trace Elements in Human Animal Nutrition.in: Academic Press, Inc, New York1971: 208
- The effect of zinc deficiency on the immune response.in: Zinc Metabolism: Current Aspects in Health and Disease. Alan R. Liss, Inc, New York1977: 143
- Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice.in: ed. 3. Proc Natl Acad Sci USA. 76. 1979: 457
- The effect of restricted dietary intake on the antibody mediated response of the zinc deficient A/J mouse.J Nutr. 1978; 108: 881
- Zinc therapy of depressed cellular immunity in acrodermatitis enteropathica.Am J Dis Child. 1979; 133: 915
- Biochemical, skeletal and allometric changes due to zinc deficiency in the baby pig.J Nutr. 1968; 95: 278
- The effect of zinc on calves with hereditary thymus hypoplasia (Lethal Trait A 46).Acta Pathol Microbiol Scand [A]. 1971; 79: 686
- Altered thymic structure and mitogen responsiveness in postnatally zinc-deprived mice.Dev Comp Immunol. 1979; 3: 725
- Circulating thymic hormone levels in zinc deficiency.Cell Immunol. 1979; 47: 100
- Regeneration of T-cell helper function in zinc-deficient adult mice.in: ed. 3. Proc Natl Acad Sci USA. 75. 1978: 5660
- Cell-mediated cytotoxicity and tumor growth in zinc-deficient mice.in: ed. 3. Proc Soc Exp Biol Med. 167. 1981: 333
- Single nutrient deficiency and cell-mediated immune responses.Am J Clin Nutr. 1980; 33: 736
- Zinc correction of defective chemotaxis in acrodermatitis enteropathica.Arch Dermatol. 1977; 113: 422
- Severe zinc deficiency in humans: association with a reversible T-lymphocyte dysfunction.Ann Intern Med. 1981; 95: 154
- Abnormal cellular immune responses during acquired zinc deficiency.Am J Clin Nutr. 1979; 32: 1466
- Kinetics of the Zn2+-stimulation of human peripheral lymphocytes in vitro.in: ed. 3. Proc Soc Exp Biol Med. 137. 1971: 1089
- Influence of oral zinc supplementation on the lymphocyte response to mitogens of normal subjects.Am J Clin Nutr. 1981; 34: 88
- Effect of zinc on peritoneal macrophages in vitro.Infect Immun. 1977; 16: 367
- Effect of zinc on the viability and phagocytic capacity of peritoneal macrophages.in: ed. 3. Proc Soc Exp Biol Med. 142. 1973: 1123
- Zinc requirement for DNA replication in stimulated human lymphocytes.J Cell Biol. 1973; 58: 594
- Effects of ethylenediaminetetraacetic acid and 1,10-phenanthroline on cell proliferation and DNA synthesis of Ehrlich ascites cells.Cancer Res. 1980; 40: 4092
- Influence of 1,10-phenanthroline on liver tumorigenesis.Res Commun Chem Pathol Pharmacol. 1972; 3: 383
- Severe zinc deficiency presenting with acrodermatitis during hyperalimentation: diagnosis, pathogenesis and treatment.J Clin Gastroenterol. 1980; 2: 1125
- Regulation of human natural killing. I. The role of monocytes, interferon and prostaglandins.J Immunol. 1981; 127: 2007
- Natural cytotoxic reactivity of human lymphocytes against a myeloid cell line: characterization of effector cells.J Immunol. 1977; 118: 355
- Destruction of human lymphoid tissue culture cell lines by human peripheral blood lymphocytes in 51Cr release cellular cytotoxicity.JNCI. 1974; 52: 345
- A multipotential leukemia cell line (K562) of human origin.in: ed. 3. Proc Soc Exp Biol Med. 166. 1981: 546
- Human monocyte-induced tumor cell cytotoxicity.Blood. 1978; 52: 211
- Lysozyme enhances monocytemediated tumoricidal activity: a potential amplifying mechanism of tumor killing.Blood. 1981; 58: 994
- Electron microscopic and functional aspects of human lymphocyte response to mitogens.Transplant Rev. 1972; 11: 39
- Detection of endotoxin in human blood and demonstration of an inhibitor.J Lab Clin Med. 1970; 75: 903
- Functional analysis of human T-cell subsets defined by monoclonal antibodies. I. Collaborative T-T interactions in the immunoregulation of B cell differentiation.J Immunol. 1980; 125: 2402
- Separation of functional subsets of human T cells by a monoclonal antibody.in: ed. 3. Proc Natl Acad Sci USA. 76. 1979: 4061
- The effect of severe zinc deficiency on serum levels of albumin, transferrin and prealbumin in man.Am J Clin Nutr. 1981; 34: 1655
- An evaluation of upper arm measurements used in nutritional assessment.Am J Clin Nutr. 1979; 32: 2136
- Chromium deficiency, glucose intolerance and neuropathy reversed by chromium supplementation in a patient receiving long-term total parenteral nutrition.Am J Clin Nutr. 1977; 30: 531
- Selenium deficiency in total parenteral nutrition.Am J Clin Nutr. 1979; 32: 2076
- On the assessment of zinc and copper nutriture in man.Am J Clin Nutr. 1979; 32: 856
- Lethal strain A 46 in cattle. Immunological investigations.Nord Vet Med. 1974; 26: 279
- Mineral deficiency effects on the generation of cytotoxic T-cells and T-helper cell factors in vitro.J Nutr. 1981; 111: 907
- The differential sensitivity of T-cell and T-cell mitogenesis to in vitro zinc deficiency.Cell Immunol. 1981; 60: 203
- Ortho-phenanthroline inhibition of DNA synthesis in mammalian cells.Exp Cell Res. 1975; 96: 145
- Effects of 1,10-phenanthroline and a zinc complex of 1,10-phenanthroline on nucleic acid synthesis in mouse liver and spleen.J Pharmacol Exp Ther. 1978; 205: 27
- Zinc deficiency and growth or Ehrlich ascites tumor.Cancer Res. 1979; 39: 2451
- Inhibition of E. coli DNA polymerase I by 1,10-phenanthroline.Biochem Biophys Res Commun. 1977; 78: 170
- Degradation of DNA by 1,10-phenanthroline.Biochem Biophys Res Commun. 1980; 93: 264
- Natural cell-mediated immunity.Adv Cancer Res. 1978; 27: 305
- Herberman RB Natural Cell-mediated Immunity Against Tumors. Academic Press, Inc, New York1980
- Natural killer (NK) cell activity in the rat. I. Isolation and characterization of the effector cells.J Immunol. 1981; 127: 282
- Expression of metastatic potential of tumor cells in young nude mice is correlated with low levels of natural killer cell-mediated cytotoxicity.Int J Cancer. 1980; 26: 675
- Chediak-Higashi gene in humans. I. Impairment of natural killer function.J Exp Med. 1980; 151: 1039
- Immunocompetent cells in patients with malignant disease. I. The lack of naturally occurring killer cell activity in the unfractionated circulating lymphocytes from patients with chronic lymphocytic leukemia.Cancer. 1976; 38: 2274
- Studies of the functions of natural killer-interferon system in patients with Sjogren syndrome.J Clin Invest. 1982; 69: 581
- Natural cell-mediated cytotoxicity in systemic lupus erythematosus: suppression by antilymphocyte antibody.Arthritis Rheum. 1980; 23: 1274
- Decline of natural nonselective cell-mediated autotoxicity in patients with tumor progression.Cancer Res. 1977; 37: 413
- Human pulmonary macrophage tumor cell cytotoxicity.Blood. 1980; 55: 612
- Defective monocyte killing in patients with malignancies and restoration of function during chemotherapy.Lancet. 1980; 2: 1102
- Effects of cadium, lead and zinc on macrophage-mediated cytotoxicity toward tumor cells.Environ Res. 1982; 28: 154
Article info
Publication history
Accepted:
June 7,
1983
Received:
October 27,
1982
Footnotes
☆Supported in part by funds from the Merit Review Funds of the Veterans Administration, a grant from the American Cancer Society (IN-13-T-1), and a grant from the Minnesota Medical Foundation.
Identification
Copyright
© 1983 Published by Elsevier Inc.
