Volume 5, Number 3—June 1999
Iron Loading and Disease Surveillance
|Transferrin in plasma, lymph, cerebrospinal fluid|
|Lactoferrin in secretions of lachrymal and mammary glands and of respiratory, gastrointestinal, and genital tracts|
|Ferritin within host cells|
|Processes induced at time of invasion|
|Suppression of assimilation of 80% of dietary irona|
|Suppression of iron efflux from macrophages that have digested effete erythrocytes to result in 70% reduction in plasma irona|
|Increased synthesis of ferritin to sequester withheld irona|
|Release of neutrophils from bone marrow into circulation and then into site of infectiona|
|Release of apolactoferrin from neutrophil granules followed by binding of iron in septic sites|
|Macrophage scavenging of ferrated lactoferrin in areas of sepsis and of tumor cell clusters|
|Hepatic release of haptoglobin and hemopexin (to bind extravasated hemoglobin and hemin, respectively)|
|Synthesis of nitric oxide (from L-arginine) by macrophages to disrupt iron metabolism of invadersb|
|Suppression of growth of microbial cells within macrophages via downshift of expression of transferrin receptors and enhanced synthesis of Nrampl (23) by the host cellsb|
|Induction in B lymphocytes of synthesis of immunoglobulins to iron-repressible cell surface proteins that bine either heme, ferrated siderophilins, or ferrated siderophores|
aActivated by interleukin-1 or -6 or by tumor necrosis factor-.
bActivated by interferon-g.
- Kontoghiorghes GJ, Weinberg ED. Iron: mammalian defense systems, mechanisms of disease, and chelation therapy approaches. Blood Rev. 1995;9:33–45.
- Weinberg ED, Weinberg GA. The role of iron in infection. Curr Opin Infect Dis. 1995;8:164–9.
- Weinberg ED. The role of iron in cancer. Eur J Cancer Prev. 1996;5:19–36.
- Connor JR, Beard JL. Dietary iron supplements in the elderly: to use or not to use? Nutr Today. 1997;32:102–9.
- Tuomainen T-P, Punnonen K, Nyyssonen K, Salonen JT. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation. 1998;97:1461–6.
- McCord JM. Effects of positive iron status at a cellular level. Nutr Rev. 1996;54:85–8.
- Weinberg ED. Patho-ecological implications of microbial acquisition of host iron. Reviews in Medical Microbiology. 1998;9:171–8.
- Weinberg ED. Acquisition of iron and other nutrients in vivo. In: Roth JA, Bolin CA, Brogdon KA, Wannemuehler MJ, editors. Virulence mechanisms of bacterial pathogens. Washington: American Society for Microbiology; 1995. p. 79-94.
- Ogunnariwo JA, Cheng C, Ford J, Schryvers AB. Response of Haemophilus somnus to iron limitation: expression and identification of a bovine-specific transferrin receptor. Microb Pathog. 1990;9:397–406.
- Arko RJ. Animal models for Neisseria species. Clin Microbiol Rev. 1989;2:S56–9.
- Gray-Owen SD, Schryvers AB. The interaction of primate transferrins with receptors on bacteria pathogenic to humans. Microb Pathog. 1993;14:389–98.
- Gonzalez GC, Casmano OL, Schryvers AB. Identification and characterization of a porcine-specific transferrin receptor in Actinobacillus pleuropneumoniae. Mol Microbiol. 1990;4:1173–9.
- Worst DJ. Iron acquisition by Helicobacter pylori. Ph.D. thesis. Amsterdam: Vrije Universiteit; 1997; p. 109-16.
- Modun B, Evans RW, Joannou CL, Williams P. Receptor-mediated recognition and uptake of iron from human transferrin by Staphylococcus aureus and Staphylococcus epidermidis. Infect Immun. 1998;65:1944–8.
- Lindsay JA, Riley TV. Staphylococcal iron requirements, siderophore production, and iron-regulated protein expression. Infect Immun. 1994;62:2309–14.
- Courcol RJ, Trivier D, Bissinger M-C, Martin GR, Brown MRW. Siderophore production by Staphylococcus aureus and identification of iron-regulated proteins. Infect Immun. 1997;65:1944–8.
- Eichenbaum Z, Muller E, Morse SA, Scott JR. Acquisition of iron from host proteins by the group A streptococcus. Infect Immun. 1996;64:5428–9.
- Coulanges V, Andre P, Vidon DJ-M. Effect of siderophores, catecholamines, and catechol compounds on Listeria spp. growth in iron-complexed medium. Biochem Biophys Res Commun. 1998;24:526–30.
- Tsolis RM, Baumler AJ, Heffron F, Stojikovic I. Contributions of TonB- and feo-mediated iron uptake to growth of Salmonella typhimurium in the mouse. Infect Immun. 1996;64:4549–56.
- Fortier AH, Leiby DA, Narayanan RB, Asafoadjei E, Crawford RM, Nacy CA, . Growth of Francisella tularensis LVS in macrophages: the acidic intracellular compartment provides essential iron required for growth. Infect Immun. 1995;63:1478–83.
- Byrd TF. Cytokines and legionellosis. Biotherapy. 1994;7:179–86.
- Barnewall RE, Rikihisa Y, Lee EH. Ehrlichia chaffeensis inclusions are early endosomes which selectively accumulate transferrin receptor. Infect Immun. 1997;65:1455–61.
- Gomes MS, Appelberg R. Evidence for a link between iron metabolism and Nrampl gene function in innate resistance against Mycobacterium avium. Immunology. 1998;95:165–8.
- Jiang X, Baldwin CL. Iron augments macrophage-mediated killing of Brucella abortus alone and in conjunction with interferon. Cell Immunol. 1993;148:397–407.
- Saleppico S, Mazzolla R, Boelaert JR, Puliti M, Barluzzi R, Bistoni F, Iron regulates microglial cell-mediated secretory and effector functions. Cell Immunol. 1996;170:251–9.
- Ghio AJ, Piantadosi CA, Crumbliss AL. Hypothesis: iron chelation plays a vital role in neutrophilic inflammation. Biometals. 1997;19:135–42.
- Hoepelman IM, Bezemer WA, Vandenbroucke-Grauls CMJE, Marx JJM, Verhoef J. Bacterial iron enhances oxygen radical-mediated killing of Staphylococcus aureus by phagocytes. Infect Immun. 1990;58:26–31.
- Delanghe JR, Langlois MR, Boelaert Jr, Van Acker J, Van Wanzeele F, van der Groen G, . Haptoglobin polymorphism, iron metabolism and mortality in HIV infection. AIDS. 1998;12:1027–32.
- Witte DL, Crosby WH, Edwards CQ, Fairbanks VF, Mitros FA. Hereditary hemochromatosis. Clin Chim Acta. 1996;245:139–200.
- Shapiro RL, Altekruse S, Hutwagner L, Bishop R, Hammond R, Wilson S, The role of Gulf Coast oysters harvested in warmer months in Vibrio vulnificus infections in the United States, 1988-1996. J Infect Dis. 1998;178:752–9.
- Weinberg ED. DF-2 sepsis: a sequela of sideremia? Med Hypotheses. 1987;24:287–9.
- Meyers DG, Strickland D, Maloley PA, Seburg JK, Wilson JE, McManus BF. Possible association of a reduction in cardiovascular events with blood donation. Heart. 1997;78:188–93.
- Kiechl S, Willeit J, Egger G, Poewe W, Oberhollenzer F. Body iron stores and the risk of carotid atherosclerosis. Prospective results from the Bruuneck study. Circulation. 1997;96:3300–7.
- Merk K, Mattson B, Mattson A, Holm G, Gullbring B, Bjorkholm M. The incidence of cancer among blood donors. Int J Epidemiol. 1990;19:505–9.
- Bonkovsky HL, Banner BF, Rothman AL. Iron and chronic viral hepatitis. Hepatology. 1997;26:759–68.
- Chitambar CR, Narasimhan J. Targeting iron-dependent DNA synthesis with gallium and transferrin-gallium. Pathobiology. 1991;59:3–10.
- Kemp JD. Iron deprivation and cancer: a view beginning with studies of monoclonal antibodies against the transferrin receptor. Histol Histopathol. 1997;12:291–6.
- Guillen C, McInnes IB, Kruger H, Brock JH. Iron, lactoferrin-and iron regulatory protein activity in the synovium; relative importance of iron loading and the inflammatory response. Ann Rheum Dis. 1998;57:309–14.
- Ward PP, Piddington CS, Cunningham GA, Zhou X, Wyatt RD, Conneely OM. A system for production of commercial quantities of human lactoferrin, a broad spectrum natural antibiotic. Biotechnology. 1995;13:498–503.
- Andrews NC, Levy JE. Iron is hot: an update on the pathophysiology of hemochromatosis. Blood. 1998;92:1845–51.
- Myers LE, Yang Y-P, Du R-P, Wang Q, Harkness RE, Schryvers AB, The transferrin binding protein B of Moraxella catarrhalis elicits bactericidal antibodies and is a potential vaccine antigen. Infect Immun. 1998;66:4183–92.
- Lissolo L, Maitre-Wilmotte G, Dumas P, Mignon M, Danve B. QuentinMillet M-J. Evaluation of transferrin-binding protein 2 within the transferrin-binding complex as a potential antigen for future meningococcal vaccines. Infect Immun. 1995;63:884–90.
- Pintor M, Ferron L, Gomez JA, Powell NBL, Ala `Aldeen DAA, Boriello SP, . Blocking of iron uptake from transferrin by antibodies against the transferrin binding proteins in Neisseria meningitidis. Microb Pathog. 1996;20:127–39.
- Lorber B. Are all diseases infectious? Ann Intern Med. 1996;125:844–51.
- Relman DA. Detection and identification of previously unrecognized microbial pathogens. Emerg Infect Dis. 1998;4:382–9.
- Cassell GH. Infectious causes of chronic inflammatory diseases and cancer. Emerg Infect Dis. 1998;4:475–87.
- Morris CJ, Earl JR, Trenam CW, Bkaje DR. Reactive oxygen species and irona dangerous partnership in inflammation. Int J Biochem Cell Biol. 1995;27:109–22.
- Tuomainen T-P, Nyyssonen K, Salonen R, Tervahauta A, Korpela H, Lakka T, Body iron stores are associated with serum insulin and blood glucose concentrations. Diabetes Care. 1997;20:426–8.
- Campbell LA, Kuo C-C, Grayston JT. Chlamydia pneumoniae and cardiovascular disease. Emerg Infect Dis. 1998;4:571–9.
- Freidank HM, Billing H. Influence of iron restriction on the growth of Chlamydia pneumoniae TWAR and Chlamydia trachomatis. Clinical Microbiology and Infection 1997;3 Suppl 2:193.23
Page created: December 10, 2010
Page updated: December 10, 2010
Page reviewed: December 10, 2010
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.