Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-05T22:27:33.124Z Has data issue: false hasContentIssue false

Cellular and molecular aspects of iron and immune function

Published online by Cambridge University Press:  28 February 2007

Jeremy H. Brock*
Affiliation:
Department of Immunology, Western Infirmary, Glasgow G11 6NT, UK
Victoriano Mulero
Affiliation:
Facultad de Biología, Universidad de Murcia, Murcia, Spain
*
*Corresponding author: Dr Jeremy H. Brock, fax +44 141 337 3217, email [email protected]
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.

Fe plays a critical role in the immune system and defence against infection. However, many aspects of the way in which Fe influences these processes at the molecular and cellular level are unclear. The present review summarizes the role of Fe in lymphocyte activation and proliferation, and discusses how Fe is handled by macrophages.

Type
Meeting Report
Copyright
Copyright © The Nutrition Society 2000

References

Alcantara, O, Javors, M & Boldt, DH (1991) Induction of protein kinase C mRNA in cultured lymphoblastoid T cells by iron-transferrin but not by soluble iron. Blood 77, 12901297.CrossRefGoogle Scholar
Alcantara, O, Obeid, L, Hannun, Y & Boldt, DH (1994) Regulation of protein kinase C (PKC) expression by iron: effect of different iron compounds on PKC-α and PKC-β gene expression and the role of the 5'-flanking region of the PKC-β gene in response to ferric transferrin. Blood 84, 35103517.CrossRefGoogle ScholarPubMed
Alvarez-Hernández, X, Licéaga, J, McKay, IC & Brock, JH (1989) Induction of hypoferremia and modulation of macrophage iron metabolism by tumor necrosis factor. Laboratory Investigation 61, 319322.Google ScholarPubMed
Baker, E & Morgan, EH (1994) Iron transport. In Iron Metabolism in Health and Disease, pp. 6395 [Brock, JH, Halliday, JW, Pippard, MJ and Powell, LW, editors]. London: W.B. Saunders.Google Scholar
Bouton, C, Oliveira, L & Drapier, JC (1998) Converse modulation of IRP1 and IRP2 by immunological stimuli in murine RAW 264.7 macrophages. Journal of Biological Chemistry 273, 94039408.CrossRefGoogle ScholarPubMed
Brekelmans, P, Van Soest, P, Leenen, PJM & Van Ewijk, W (1994) Inhibition of proliferation and differentiation during early T cell development by anti-transferrin receptor antibody. European Journal of Immunology 24, 28962902.CrossRefGoogle Scholar
Brock, JH (1993) Iron and immunity. Journal of Nutritional Immunology 2, 47106.CrossRefGoogle Scholar
Byrd, TF & Horwitz, MA (1990) Interferon-gamma activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. Journal of Clinical Investigation 83, 14571465.CrossRefGoogle Scholar
Djeha, A & Brock, JH (1992) Effect of transferrin, lactoferrin and chelated iron on human T-lymphocytes. British Journal of Haematology 80, 235241.CrossRefGoogle ScholarPubMed
Drapier, JC, Hirling, H, Wietzerbin, J, Kaldy, P & Kuhn, LC (1993) Biosynthesis of nitric oxide activates iron regulatory factor in macrophages. EMBO Journal 12, 36433649.CrossRefGoogle ScholarPubMed
Drapier, JC, Pellat, C & Henry, Y (1991) Generation of EPR-detectable nitrosyl-iron complexes in tumor target cells cocultured with activated macrophages. Journal of Biological Chemistry 266, 1016210167.CrossRefGoogle ScholarPubMed
Esparza, I & Brock, JH (1981) Release of iron by resident and stimulated mouse peritoneal macrophages following ingestion and digestion of transferrin-antitransferrin immune complexes. British Journal of Haematology 49, 603614.CrossRefGoogle Scholar
Fleming, MD & Andrews, NC (1998) Mammalian iron transport: an unexpected link between metal homeostasis and host defense. Journal of Laboratory and Clinical Medicine 132, 464468.CrossRefGoogle ScholarPubMed
Freireich, EJ, Miller, A, Emerson, CP & Ross, JF (1957) The effect of inflammation on the utilization of erythrocyte and transferrin bound radioiron for red cell production. Blood 12, 972983.CrossRefGoogle Scholar
Golding, S & Young, SP (1995) Iron requirements of human lymphocytes: relative contributions of intra- and extra-cellular iron. Scandinavian Journal of Immunology 41, 229236.CrossRefGoogle ScholarPubMed
Haile, DJ (1999) Regulation of genes of iron metabolism by the iron-response proteins. American Journal of Medical Science 318, 230240.CrossRefGoogle ScholarPubMed
Jurado, RL (1997) Iron, infections, and anemia of inflammation. Clinical Infectious Diseases 25, 888895.CrossRefGoogle ScholarPubMed
Kim, S & Ponka, P (2000) Effects of interferon-gamma and lipopolysaccharide on macrophage iron metabolism are mediated by nitric oxide-induced degradation of iron regulatory protein 2. Journal of Biological Chemistry 275, 62206226.CrossRefGoogle ScholarPubMed
Kleber, EE, Lynch, SR, Skikne, B, Torrance, JD, Bothwell, TH & Charlton, RW (1978) Erythrocyte catabolism in the inflammatory peritoneal monocytes. British Journal of Haematology 39, 4154.CrossRefGoogle Scholar
Konijn, AM & Hershko, C (1977) Ferritin synthesis in inflammation. I. Pathogenesis of impaired iron release. British Journal of Haematology 37, 716.CrossRefGoogle ScholarPubMed
Kuvibidila, SR, Baliga, BS, Warrier, RP & Suskind, RM (1997) Iron deficiency reduces the hydrolysis of cell membrane phosphatidyl inositol-4,5-biphosphate during splenic lymphocyte activation in C57BL/6 mice. Journal of Nutrition 128, 10771083.CrossRefGoogle Scholar
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, 468478.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Leberman, HM, Cohen, A, Lee, JWW, Freedman, MH & Gelfand, EW (1984) Deferoxamine: a reversible S-phase inhibitor of lymphocyte proliferation. Blood 64, 748753.CrossRefGoogle Scholar
Mainou-Fowler, T & Brock, JH (1985) Effect of iron deficiency on the response of mouse lymphocytes to Concanavalin A: The importance of transferrin-bound iron. Immunology 54, 325332.Google ScholarPubMed
Miller, LL, Miller, SC, Torti, SV, Tsuji, Y & Torti, FM (1991) Iron-dependent induction of ferritin H-chain by tumor necrosis factor. Proceedings of the National Academy of Sciences USA 88, 49464950.CrossRefGoogle Scholar
Mulero, V & Brock, JH (1999) Regulation of iron metabolism in murine J774 macrophages: role of nitric oxide-dependent and -independent pathways following activation with gamma interferon and lipopolysaccharide. Blood 94, 23832389.CrossRefGoogle ScholarPubMed
Oria, R, Alvarez-Hernández, X, Licéaga, J & Brock, JH (1988) Uptake and handling of iron from transferrin, lactoferrin and immune complexes by a macrophage cell line. Biochemical Journal 252, 221225.CrossRefGoogle ScholarPubMed
Oria, R, Sánchez, L, Houston, T, Hentze, MW, Liew, FY & Brock, JH (1995) Effect of nitric oxide on expression of transferrin receptor and ferritin, and on cellular iron metabolism in K562 human erythroleukaemia cells. Blood 85, 29622966.CrossRefGoogle Scholar
Salmerón, A, Borroto, A, Fresno, M, Crumpton, MJ, Ley, S & Alarcón, B (1995) Transferrin receptor induces tyrosine phosphorylation in T cells and is physically associated with the TCR ζchain. Journal of Immunology 154, 16751683.CrossRefGoogle Scholar
Smith, A, Eskew, JD, Borza, CM, Pendrak, M & Hunt, RC (1997) Role of heme-hemopexin in human T-lymphocyte proliferation. Experimental Cell Research 232, 246254.CrossRefGoogle ScholarPubMed
Testa, U, Kuhn, L, Petrini, M, Quaranta, MT, Pelosi, E & Peschle, C (1991) Differential regulation of iron regulatory element-binding protein(s) in cell extracts of activated lymphocytes versus monocytes-macrophages. Journal of Biological Chemistry 266, 1392513930.CrossRefGoogle ScholarPubMed
Walter, T, Olivares, M, Pizarro, F & Muñoz, C (1997) Iron, anemia, and infection. Nutrition Reviews 55, 111124.CrossRefGoogle ScholarPubMed
Wei, XQ, Charles, IG, Smith, A, Ure, J, Feng, GJ, Huang, FP, Xu, D, Muller, W, Moncada, S & Liew, FY (1995) Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375, 408411.CrossRefGoogle ScholarPubMed
Weiss, G, Goossen, B, Doppler, W, Fuchs, D, Pantopoulos, K, Werner-Felmayer, G, Wachter, H & Hentze, MW (1993) Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway. EMBO Journal 12, 36513657.CrossRefGoogle ScholarPubMed
Weiss, G, Wachter, H & Fuchs, D (1995) Linkage of cell-mediated immunity to iron metabolism. Immunology Today 16, 495500.CrossRefGoogle ScholarPubMed