Abstract
Lactoferrin is an iron-binding glycoprotein abundantly present in human milk, and has been postulated both to increase and to decrease intestinal iron absorption. To examine this problem, the interaction of milk iron with pup hemoglobin was studied in controls and in transgenic mice overexpressing human lactoferrin in their milk (2 lines expressing 12 mg/mL and 4 mg/mL, respectively). At day 14 of gestation, pregnant mice were switched from a diet of commercial chow containing iron at 300mg/kg to diets containing 5, 15, or 50 mg iron/kg; controls continued on chow. Nontransgenic pups were cross-fostered to transgenic dams to ensure that any results found in the pups were the effect of milk components. The hemoglobin level in the blood of 10-day-old suckling neonates was measured and calculated as total hemoglobin per pup. The total hemoglobin levels were lower in the pups receiving milk high in human lactoferrin, but the difference reached significance (P < 0.02) only at the highest level of dietary iron. Our findings do not support the hypothesis that lactoferrin functions as an intestinal iron scavenger, at least at high doses.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Azuma N, Mori H, Kaminogawa S, Yamauchi K. Stimulatory effect of human lactoferrin on DNA synthesis in BALB/c 3T3 cells. Agrie Biol Chem 1989;53:31–35.
Baker EN, Anderson BF, Baker HM, Day CL, Haridas M, Norris GE, Rumball SV, Smith CA, Thomas DH. Three-dimentional structure of lactoferrin in various states. Adv Exp Med Biol 1994;357:227–230.
Bezault J, Bhimani R, Wiprovnick J, Furmanski P. Human lactoferrin inhibits growth of solid tumors and development of experimental metastases in mice. Cancer Res 1994;54:2310–2312.
Casey CE, Smith A, Zhang P. Macrominerals in human and animal milks. In: Jensen RE, editor. Handbook of Milk Composition. San Diego: Academic Press; 1995. pp 87–98.
Davidson LA, Lonnerdal B. Lactoferrin and secretory IgA in the feces of exclusively breast-fed infants. Am J Clin Nutr 1987;41:852–861.
Davidson LA, Lonnerdal B. Fe-saturation and proteolysis of human lactoferrin: effect on brush-border receptor-mediated uptake of Fe and Mn. Am J Physiol 1989;257:G390–G394.
Davidson LA, Litov RE, Lonnerdal B. Iron retention from lactoferrin supplemented formulas in infant rhesus monkeys. Pediatr Res 1990;27:170–180.
Davidson LA, Kastenmayer P, Yuen M, Lonnerdal B, Hurrell RE Influence of lactoferrin on iron absorption from human milk in infants. Pediatr Res 1994;35:117–124.
Dewey KG, Lonnerdal B. Milk and nutrient intake of breast-fed infants from 1 to 6 months: relation to growth and fatness. J Pediatr Gastroenterol Nutr 1983;2:497–506.
Dewey KG, Finley DA, Lonnerdal B. Breast milk volume and composition during late lactation (7–20 months). J Pediatr Gastroenterol Nutr 1984;3:713–720.
Ellison RT. The effects of lactoferrin on gram-negative bacteria. Adv Exp Med Biol 1994;357:71–90. Fransson GB, Lonnerdal B. Iron in human milk J Pediatr 1980;96:380–384.
Fransson GB, Thoren-Tolling K, Jones B, Hambracus I, Lonnerdal B. Absorption of lactoferrin iron in suckling pigs. Nutr Res 1983a;3:373–384.
Fransson GB, Keen CI, Lonnerdal B. Supplementation of milk with iron bound to lactoferrin using weanling mice. I. Effects on hematology and tissue iron. J Pediatr Gastroenterol Nutr 1983b;2:693–700.
Goldman AS, Garza C, Schanler RJ, Goldblum RM. Molecular forms of lactoferrin in the stool and urine from infants fed human milk. Pediatr Res 1990;27:252–255.
Hashizume S, Kuroda K, Murakami H. Identification of lactoferrin as an essential growth factor for human lymphocytic cell lines in serum-free medium. Biochim Biophys Acta 1983;763:377–382.
Hennart PF, Brasseur DJ, Delogne-Desnoeck JB, Dramaix MM, Robyn CE. Lysozyme, lactoferrin and secretory immunoglobulin A content in breast milk: influence of duration of lactation, nutritional status, prolactin status and parity of mother. Am J Clin Nutr 1991;53:32–39.
Hu WI, Mazurier J, Montreuil J, Spik G. Isolation and partial characterization of a lactotransferrin receptor from mouse intestinal brush border. Biochemistry 1990;29:535–541.
Iyer S, Lonnerdal B. Lactoferrin, lactoferrin receptors and iron metabolism. Eur J Clin Nutr 1993; 47:232–241.
Kume S, Tanabe S. Effect of twinning and supplemental iron-saturated lactoferrin on iron status of newborn calves. J Dairy Sci 1994;77:118–123.
Kume S, Tanabe S. Effect of supplemental lactoferrin with ferrous iron on iron status of newborn calves. J Dairy Sci 1996;79:459–464.
Lonnerdal B. Iron in breast milk. In: Stekel A, editor. Iron Nutrition in Infancy and Childhood. Volume 4, Nestlé Nutrition Workshop Series. New York: Raven Press; 1984. pp. 95–118.
Lonnerdal B. Effects of milk and milk components on calcium, magnesium, and trace element absorption during infancy. Physiol Rev 1997;77:643–669.
Lonnerdal B, Iyer S. Lactoferrin: molecular structure and biological function. Annu Rev Nutr 1995; 15:93–110.
Masson PL, Heremans JF. Lactoferrin in milk from different species. Comp Biochem Physiol [B] 1971; 39:119–129.
Mazurier J, Montreuil J, Spika G. Visualization of lactotransferrin brush-border receptors by ligand blotting. Biochim Biophys Acta 1985;821:453–460.
Neville MC, Chatfield K, Hanson L, Lewis A, Monks J, Nuijens J, 011ivier-Bousquet M, Schanbacher F, Sawicki V, Zhang P. Lactoferrin secretion into mouse milk. Development of secretory activity, the localization of lactoferrin in the secretory pathway, and interactions of lactoferrin with milk iron. Adv Exp Med Biol 1998;443:141–153.
Nichols BL, McKee KS, Henry JF, Putman M. Human lactoferrin stimulates thymidine incorporation into DNA of rat crypt cells. Pediatr Res 1987;21:563–567.
Nichols BL, McKee KS, Hubers HA. Iron is not required in the lactoferrin stimulation of thymidine incorporation into the DNA of rat crypt enterocytes. Pediatr Res 1990;27:525–528.
Nuijens JH, van Berkel PHC, Schanbacher FL. Structure and biological actions of lactoferrin. J Mammary Gland Biol Neoplasia 1996;1:285–295.
Nuijens JH, van Berke] PH, Geerts ME, Hartevelt PP, de Boer HA, van Veen HA, Pieper FR. Characterization of recombinant human lactoferrin secreted in milk of transgenic mice. J Biol Chem 1997; 272:8802–8807.
Oguchi S, Walker WA, Sanderson IR. Iron saturation alters the effect of lactoferrin on the proliferation and differentiation of human enterocytes (Caco-2 cells). Biol Neonate 1995;67:330–339.
Prentice A, Ewing G, Roberts SB, Lucas A, MacCarthy A, Jarjou LM, Whitehead RG. The nutritional role of breast milk IgA and lactoferrin. Acta Pediatr Scand 1987;76:592–598.
Sanchez L, Ismail M, Liew FY, Brock JH. Iron transport across Caco-2 monolayers. Effect of transferrin, lactoferrin and nitric oxide. Biochim Biophys Acta 1996;1289:291–297.
Schanler R, Goldblum R, Garza C, Goldman AS. Enhanced fecal excretion of selected immune factors in very low birth weight infants. Pediatr Res 1986;20:711–715.
Slimes MA, Vuori E, Kuitunen P. Breast milk iron: a declining concentration during the course of lactation. Acta Paediatr Scand 1979;68:29–31.
Spik G, Brunet B, Mazunier-Dehaine C, Fontaine G, Montreuil T. Characterization and properties of the human and bovine lactotransferrins extracted from the feces of newborn infants. Acta Pediatr Scand 1982;71:979–985.
Yoo YC, Watanabe S, Watanabe R, Hata K, Shimazaki K, Azuma I. Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibits tumor metastasis in mice. Jpn J Can Res 1997; 88:184–190.
Zhang P, Sawicki V, Lewis A, Hanson L, Monks J, Neville MC. The effect of serum iron concentration on iron secretion into mouse milk. J Physiol 2000;522(Pt 3):479–491.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer Science+Business Media New York
About this chapter
Cite this chapter
Hanson, L.H., Sawicki, V., Lewis, A., Nuijens, J.H., Neville, M.C., Zhang, P. (2001). Does Human Lactoferrin in the Milk of Transgenic Mice Deliver Iron to Suckling Neonates?. In: Newburg, D.S. (eds) Bioactive Components of Human Milk. Advances in Experimental Medicine and Biology, vol 501. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1371-1_29
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1371-1_29
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5521-2
Online ISBN: 978-1-4615-1371-1
eBook Packages: Springer Book Archive