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Reduced thymocyte proliferation but not increased apoptosis as a possible cause of thymus atrophy in iron-deficient mice

Published online by Cambridge University Press:  09 March 2007

Solo R. Kuvibidila ,
Connie Porretta ,
B. Surendra Baliga  and
Lily E. Leiva
Solo R. Kuvibidila*
Affiliation:
Department of Pediatrics, Divisions of Hematology/Oncology and Allergy/Immunology, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans LA 70112, USA
Connie Porretta
Affiliation:
Department of Pulmonary Medicine, Louisiana State University, Health Sciences Center, 1542 Tulane Avenue, New Orleans LA 70112, USA
B. Surendra Baliga
Affiliation:
Department of Pediatrics, University of South Alabama College of Medicine, 2451 Fillingim Street, Mobile AL 36617, USA
Lily E. Leiva
Affiliation:
Department of Pediatrics, Divisions of Hematology/Oncology and Allergy/Immunology, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans LA 70112, USA
*
*Corresponding author: Dr S. R. Kuvibidila, fax +1 504 568 3078, email skuvib@lsuhsc.edu
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Abstract

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Iron deficiency induces thymus atrophy in laboratory animals and very likely in humans by unknown mechanisms. The atrophy is associated with impaired cell-mediated immunity. In this study, we tested the hypothesis that thymus atrophy is a result of increased apoptosis and reduced thymocyte proliferation. Thymocytes were obtained from twenty-seven control, twenty-seven pairfed, twenty-seven iron-deficient (ID) mice; twelve and fourteen ID mice that received the control diet (0·9 mmol/kg versus 0·09 mmol/kg for the ID diet) for 1 d (repletion, R1) and 3 d (R3), respectively. Cell cycle analysis and apoptosis were studied by flow cytometry using propidium iodide staining and terminal deoxyuridine nick end labeling of DNA breaks assay respectively. When mice were killed, haemoglobin, haematocrit, and liver iron stores of ID, R1, and R3 mice were 25–40 % of those of control and pairfed mice (P<0·01). Absolute and relative thymus weights and thymocyte numbers were 19 to 68 % lower in ID, R1, and R3 than in control and pairfed groups (P<0·05). We found no significant difference among groups in the percentage of cells undergoing apoptosis. A higher percentage of thymocytes from ID and R1 mice than those of control, pairfed, and R3 mice were in the resting phase of the normal cell cycle (P<0·05). Conversely, a lower percentage of thymocytes from ID and R1 mice than those from control, pairfed, and R3 mice were in the DNA synthesis phase and late phase of DNA synthesis and onset of mitosis (G2-M) (P<0·05). Indicators of iron status positively correlated (r 0·3 to 0·56) with the percentage of thymocytes in the G2-M phase (P<0·05). Results suggest that reduced cell proliferation but not increased apoptosis is the cause of thymus atrophy associated with iron deficiency.

Keywords

Iron deficiencyHaemoglobinThymus atrophyCell cycle analysis
Type
Research Article
Information
British Journal of Nutrition , Volume 86 , Issue 2 , August 2001 , pp. 157 - 162
Copyright
Copyright © The Nutrition Society 2001

References

Abbas, AK, Lichtman, AH & Pober, JS, (1997) T cell maturation in the thymus. In Cellular and Molecular Immunology pp. 171–193 [Abbas, AK, Lichtman, AH and Pober, JS, editors]. Philadelphia, PA: WB Saunders.Google Scholar
Alleyne, GA & Young, VH (1967) Adrenocortical function in children with severe protein-calorie malnutrition. Clinical Science 33, 189–200.Google Scholar
Becker, DJ (1983) The endocrine responses to protein-calorie malnutrition. Annual Review of Nutrition 3, 187–212.CrossRefGoogle ScholarPubMed
Chandra, RK & Newberne, PM (1977) Nutrition, Immunity, and Infection. New York, NY: Plenum Press.CrossRefGoogle Scholar
Coligan, JJ, Kruisbeek, AM, Margulies, DH, Shevalies, EM & Strober, W editors (1991) Current Protocols in Immunology, Section 5.7. New York, NY: Greene Publishing Associates and Wiley-Interscience.Google Scholar
DePascal-Jardieu, P & Fraker, PJ (1979) The role of corticosterone in the loss in immune function in zinc-deficient A/J mouse. Journal of Nutrition 109, 1847–1855.CrossRefGoogle Scholar
Fukuchi, K, Tomoyasu, S, Watanabe, H, Kaetsu, S, Tsuruoka, N & Gomi, K (1995) Iron deprivation results in an increase in p53 expression. Biological Chemistry (Hoppe Seyler) 376, 627–630.Google Scholar
Hileti, D, Panayiotidis, P & Hoffbrand, AV (1995) Iron chelators induce apoptosis in proliferating cells. British Journal of Haematology 89, 181–187.CrossRefGoogle ScholarPubMed
Haq, RU, Wereley, JP & Chitambar, CR (1995) Induction of apoptosis by iron deprivation in human leukemic CCRF-CEM cells. Experimental Hematology 23, 428–432.Google ScholarPubMed
Kochanowiski, BA & Sherman, AR (1982) Serum and secretory proteins in iron-deficient rat pups and dams. Nutrition Research 2, 689–698.CrossRefGoogle Scholar
Kuvibidila, S, Baliga, BS & Suskind, RM (1982) Generation of plaque-forming cells in iron deficient anemic. Nutrition Reports International 26, 861–872.Google Scholar
Kuvibidila, S, Dardenne, M, Savino, W & Lepol, F (1990) Influence of iron deficiency anemia on selected thymus functions in mice: thymulin biological activity, T-cell subsets, and thymocyte proliferation. American Journal of Clinical Nutrition 51, 228–232.CrossRefGoogle ScholarPubMed
Kuvibidila, S, Yu, L, Ode, D & Warrier, RP (1993) The immune response in protein-energy malnutrition and single nutrient deficiencies. In Human Nutrition: a Comprehensive Treatise Vol. 8, pp. 121–155 [Klufeld, DM, editor]. New York, NY: Plenum Press.Google Scholar
Kuvibidila, S, Baliga, BS, Warrier, RP & Suskind, RM (1998) Iron deficiency reduces the hydrolysis of cell membrane phosphatidyl inositol-4-5-bisphosphate during splenic lymphocyte activation in C57BL/6 mice. Journal of Nutrition 128, 1077–1083.CrossRefGoogle ScholarPubMed
Kuvibidila, SR, Kitchens, D & Baliga, BS (1999) In vivo and in vitro iron-deficiency reduces protein kinase C activity and translocation in murine splenic and purified T cells. Journal of Cellular Biochemistry 74, 468–478.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Nauss, KN, Mark, D & Suskind, RM (1979) The effect of vitamin A deficiency on the in vitro cellular immune response of rats. Journal of Nutrition 109, 1815–1823.CrossRefGoogle ScholarPubMed
Munro, BH, Visintainer, MA & Page, EB, (1986) Differences among group means: one-way analysis: oneway analysis of variance. In Statistical Methods for Health Care Research, 1st edition, pp. 174–199 [Munro, BH, Visintainer, MA and Page, EB, editors]. Philadelphia, PA: JB Lippincott Company.Google Scholar
Rodak, BF (1992) Routine laboratory evaluation of erythrocytes. In Clinical Hematology: Principles, Procedures, Correlations, pp.97–127 [Lotspeich-Steininger, CA, Stiene-Martin, EA and Koepke, JA, editors]. Philadelphia, PA: JB Lippincott Company.Google Scholar
Smith, HF, Latham, MC, Azaburke, JA, Butler, WR, Phillips, LS, Pond, WG & Enwonwu, CO (1981) Blood plasma levels of cortisol, insulin, growth hormone, and somatomedin in children with marasmus, kwashiorkor, and intermediate forms of protein-energy malnutrition. Proceedings of the Society of Experimental Biology and Medicine 167, 607–611.CrossRefGoogle ScholarPubMed
Smythe, PM, Scholnland, M, Brereton-Stiles, G, Coovadra, HM, Grace, HJ, Loening, WE, Mafoyane, A, Parent, MA & Vos, GA (1971) Thymolymphatic deficiency and expression of cell mediated immunity in protein-calorie malnutrition. Lancet 2, 939–944.CrossRefGoogle Scholar
Sunderman, FW Jr (1995) The influence of zinc on apoptosis. Annals of Clinical and Laboratory Science 25, 134–242.Google ScholarPubMed