Skip to main content
SpringerLink
Log in

Lactoferrin

  • Chapter
  • First Online:
Advanced Dairy Chemistry

Abstract

Lactoferrin is an iron-binding protein which is present in high concentrations in human milk. It is also present in bovine milk, albeit in low concentration. Lactoferrin has been shown to have bacteriostasis/bactericidal effects, being a component of the immune system, a growth factor, and an enhancer of iron absorption. These possible biological functions have led to interest in commercial applications of lactoferrin, and purified bovine lactoferrin and human recombinant lactoferrin are now available in large quantities. Lactoferrin has received attention as an additive in infant formulas, food supplements, and other health-benefit products. Various clinical trials to evaluate the efficacy of human recombinant or bovine lactoferrin have been conducted, showing feasibility of this multifunctional glycoprotein for pharmaceutical purposes in several diseases such as cancer, periodontal disorders, and wound healing.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ainscough, E.W., Brodie, A.M. and Plowman, J.E. (1979). The chromium, manganese, cobalt and copper complexes of human lactoferrin. Inorg. Chim. Acta 33, 145–153.

    Google Scholar 

  • Ammons, M.C., Ward, L.S., Fisher, S.T., Wolcott, R.D. and James, G.A. (2009). In vitro susceptibility of established biofilms composed of a clinical wound isolate of Pseudomonas aeruginosa treated with lactoferrin and xylitol. Int. J. Antimicrob. Agents 33, 230–236.

    Google Scholar 

  • Amouric, M., Marvaldi, J., Pichon, J., Bellot, F. and Figarella, C. (1984). Effect of lactoferrin on the growth of a human colon adenocarcinoma cell line—comparison with transferrin. In Vitro 20, 543–548.

    Google Scholar 

  • Andersen, J.H., Jenssen, H., Sandvik, K. and Gutteberg, T.J. (2004). Anti-HSV activity of lactoferrin and lactoferricin is dependent on the presence of heparan sulphate at the cell surface. J. Med. Virol. 74, 262–271.

    Google Scholar 

  • Anderson, B.F., Baker, H.M., Norris, G.E., Rice, D.W. and Baker, E.N. (1989). Structure of human lactoferrin: crystallographic structure analysis and refinement at 2.8 Å resolution. J. Mol. Biol. 209, 711–734.

    Google Scholar 

  • Ando, K., Hasegawa, K., Shindo, K., Furusawa, T., Fujino, T., Kikugawa, K., Nakano, H., Takeuchi, O., Akira, S., Akiyama, T., Gohda, J., Inoue, J. and Hayakawa, M. (2010). Human lactoferrin activates NF-kappaB through the Toll-like receptor 4 pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling. FEBS J. 277, 2051–2066.

    Google Scholar 

  • Arnold, D., Di Biase, A.M., Marchetti, M., Pietrantoni, A., Valenti, P., Seganti, L. and Superti, F. (2002). Antiadenovirus activity of milk proteins: lactoferrin prevents viral infection. Antiviral Res. 53, 153–158.

    Google Scholar 

  • Arslan, S.Y., Leung, K.P. and Wu, C.D. (2009). The effect of lactoferrin on oral bacterial attachment. Oral Microbiol. Immunol. 24, 411–416.

    Google Scholar 

  • Baker, E.N. and Lindley, P.F. (1993). New perspectives on the structure and function of transferrins. J. Inorg. Biochem. 47, 147–160.

    Google Scholar 

  • Balmer, S.E., Scott, P.H. and Wharton, B.A. (1989). Diet and faecal flora in the newborn: lactoferrin. Arch. Dis. Child. 64, 1685–1690.

    Google Scholar 

  • Baveye, S., Elass, E., Fernig, D.G., Blanquart, C., Mazurier, J. and Legrand, D. (2000). Human lactoferrin interacts with soluble CD14 and inhibits expression of endothelial adhesion molecules, E-selectin and ICAM-1, induced by the CD14-lipopolysaccharide complex. Infect. Immun. 68, 6519–6525.

    Google Scholar 

  • Beaumont, S.L., Maggs, D.J. and Clarke, H.E. (2003). Effects of bovine lactoferrin on in vitro replication of feline herpesvirus. Vet. Ophthalmol. 6, 245–250.

    Google Scholar 

  • Bellamy, W., Takase, M., Yamauchi, K., Wakabayashi, H., Kawase, K. and Tomita, M. (1992). Identification of the bactericidal domain of lactoferrin. Biochim. Biophys. Acta 1121, 130–136.

    Google Scholar 

  • Bennett, R.M. and Davis, J. (1981). Lactoferrin binding to human peripheral blood cells: an interaction with a B-enriched population of lymphocytes and a subpopulation of adherent mononuclear cells. J. Immunol. 127, 1211–1216.

    Google Scholar 

  • Berkhout, B., van Wamel, J. L., Beljaars, L., Meijer, D. K., Visser, S. and Floris, R. (2002). Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides. Antiviral Res. 55, 341–355.

    Google Scholar 

  • Berseth, C.L., Lichtenberger, L.M. and Morriss, F.H., Jr. (1983). Comparison of the gastrointestinal growth-promoting effects of rat colostrum and mature milk in newborn rats in vivo. Am. J. Clin. Nutr. 37, 52–60.

    Google Scholar 

  • Bharadwaj, S., Naidu, A.G., Betageri, G.V., Prasadarao, N.V. and Naidu, A.S. (2009). Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women. Osteoporos. Int. 20, 1603–1611.

    Google Scholar 

  • Birgens, H.S., Hansen, N.E., Karle, H. and Kristensen, L.O. (1983). Receptor binding of lactoferrin by human monocytes. Br. J. Haematol. 54, 383–391.

    Google Scholar 

  • Blais, A., Malet, A., Mikogami, T., Martin-Rouas, C. and Tome, D. (2009). Oral bovine lactoferrin improves bone status of ovariectomized mice. Am. J. Physiol. Endocrinol. Metab. 296, E1281–E1288.

    Google Scholar 

  • Blakeborough, P., Salter, D.N. and Gurr, M.I. (1983). Zinc binding in cow’s milk and human milk. Biochem. J. 209, 505–512.

    Google Scholar 

  • Bolscher, J.G., Adao, R., Nazmi, K., van den Keybus, P.A., van ‘t Hof, W., Nieuw Amerongen, A.V., Bastos, M. and Veerman, E.C. (2009). Bactericidal activity of LF chimera is stronger and less sensitive to ionic strength than its constituent lactoferricin and lactoferrampin peptides. Biochimie 91, 123–132.

    Google Scholar 

  • Bournazou, I., Pound, J.D., Duffin, R., Bournazos, S., Melville, L.A., Brown, S.B., Rossi, A.G. and Gregory, C.D. (2009). Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin. J. Clin. Invest. 119, 20–32.

    Google Scholar 

  • Boxer, L.A., Coates, T.D., Haak, R.A., Wolach, J.B., Hoffstein, S. and Baehner, R.L. (1982). Lactoferrin deficiency associated with altered granulocyte function. N. Engl. J. Med. 307, 404–410.

    Google Scholar 

  • Brines, R.D. and Brock, J.H. (1983). The effect of trypsin and chymotrypsin on the in vitro antimicrobial and iron-binding properties of lactoferrin in human milk and bovine colostrum. Unusual resistance of human apolactoferrin to proteolytic digestion. Biochim. Biophys. Acta 759, 229–235.

    Google Scholar 

  • Brock, J.H. (1985). Lactoferrin in human milk: its role in iron absorption and protection against enteric infection in the newborn infant. Arch. Dis. Child. 55, 417–421.

    Google Scholar 

  • Bullen, J.J., Rogers, H.J. and Leigh, L. (1972). Iron-binding proteins in milk and resistance to Escherichia coli infection in infants. Br. Med. J. 1, 69–75.

    Google Scholar 

  • Burrin, D.G., Wang, H., Heath, J. and Dudley, M.A. (1996). Orally administered lactoferrin increases hepatic protein synthesis in formula-fed newborn pigs. Pediatr. Res. 40, 72–76.

    Google Scholar 

  • Campbell, E.J. (1982). Human leukocyte elastase, cathepsin G, and lactoferrin: family of neutrophil granule glycoproteins that bind to an alveolar macrophage receptor. Proc. Natl. Acad. Sci. USA. 79, 6941–6945.

    Google Scholar 

  • Chierici, R., Sawatzki, G., Tamisari, L., Volpato, S. and Vigi, V. (1992). Supplementation of an adapted formula with bovine lactoferrin. 2. Effects on serum iron, ferritin and zinc levels. Acta Paediatr. 81, 475–479.

    Google Scholar 

  • Chodaczek, G., Saavedra-Molina, A., Bacsi, A., Kruzel, M.L., Sur, S. and Boldogh, I. (2007). Iron-mediated dismutation of superoxide anion augments antigen-induced allergic inflammation: effect of lactoferrin. Postepy. Hig. Med. Dosw. (Online) 61, 268–276.

    Google Scholar 

  • Cornish, J. (2004). Lactoferrin promotes bone growth. Biometals 17, 331–335.

    Google Scholar 

  • Cornish, J., Callon, K.E., Naot, D., Palmano, K.P., Banovic, T., Bava, U., Watson, M., Lin, J.M., Tong, P.C., Chen, Q., Chan, V.A., Reid, H.E., Fazzalari, N., Baker, H.M., Baker, E.N., Haggarty, N.W., Grey, A.B. and Reid, I.R. (2004). Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo. Endocrinology 145, 4366–4374.

    Google Scholar 

  • Cox, T.M., Mazurier, J., Spik, G., Montreuil, J. and Peters, T.J. (1979). Iron binding proteins and influx of iron across the duodenal brush border. Evidence for specific lactotransferrin receptors in the human intestine. Biochim. Biophys. Acta 588, 120–128.

    Google Scholar 

  • Crouch, S.P., Slater, K.J. and Fletcher, J. (1992). Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood 80, 235–240.

    Google Scholar 

  • Cumberbatch, M., Bhushan, M., Dearman, R.J., Kimber, I. and Griffiths, C.E. (2003). IL-1beta-induced Langerhans’ cell migration and TNF-alpha production in human skin: regulation by lactoferrin. Clin. Exp. Immunol. 132, 352–359.

    Google Scholar 

  • Damiens, E., El Yazidi, I., Mazurier, J., Duthille, I., Spik, G. and Boilly-Marer, Y. (1999). Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells. J. Cell Biochem. 74, 486–498.

    Google Scholar 

  • Davidson, L.A. and Lönnerdal, B. (1986). Isolation and characterization of rhesus monkey milk lactoferrin. Pediatr. Res. 20, 197–201.

    Google Scholar 

  • Davidson, L.A. and Lönnerdal, B. (1987). Persistence of human milk proteins in the breast-fed infant. Acta Paediatr. Scand. 76, 733–740.

    Google Scholar 

  • Davidson, L.A. and Lönnerdal, B. (1988). Specific binding of lactoferrin to brush-border membrane: ontogeny and effect of glycan chain. Am. J. Physiol. 254, G580–G585.

    Google Scholar 

  • Davidson, L.A. and Lönnerdal, B. (1989). Fe-saturation and proteolysis of human lactoferrin: effect on brush-border receptor-mediated uptake of Fe and Mn. Am. J. Physiol. 257, G930–G934.

    Google Scholar 

  • Davidson, L.A., Litov, R.E. and Lönnerdal, B. (1990). Iron retention from lactoferrin-supplemented formulas in infant rhesus monkeys. Pediatr. Res. 27, 176–180.

    Google Scholar 

  • Davidsson, L., Kastenmayer, P., Yuen, M., Lönnerdal, B. and Hurrell, R.F. (1994). Influence of lactoferrin on iron absorption from human milk in infants. Pediatr. Res. 35, 117–124.

    Google Scholar 

  • Dionysius, D.A. and Milne, J.M. (1997). Antibacterial peptides of bovine lactoferrin: purification and characterization. J. Dairy Sci. 80, 667–674.

    Google Scholar 

  • Donovan, S.M., Atkinson, S.A., Whyte, R.K. and Lönnerdal, B. (1989). Partition of nitrogen intake and excretion in low-birth-weight infants. Am. J. Dis. Child. 143, 1485–1491.

    Google Scholar 

  • Drescher, K., Roos, N., Pfeuffer, M., Seyfert, H.M., Schrezenmeir, J. and Hagemeister, H. (1999). Recovery of 15N-lactoferrin is higher than that of 15N-casein in the small intestine of suckling, but not adult miniature pigs. J. Nutr. 129, 1026–1030.

    Google Scholar 

  • Elass, E., Masson, M., Mazurier, J. and Legrand, D. (2002). Lactoferrin inhibits the lipopolysaccharide-induced expression and proteoglycan-binding ability of interleukin-8 in human endothelial cells. Infect. Immun. 70, 1860–1866.

    Google Scholar 

  • Ellison, R.T., 3rd and Giehl, T.J. (1991). Killing of Gram-negative bacteria by lactoferrin and lysozyme. J. Clin. Invest. 88, 1080–1091.

    Google Scholar 

  • Ellison, R.T., 3rd, Giehl, T.J. and LaForce, F.M. (1988). Damage of the outer membrane of enteric Gram-negative bacteria by lactoferrin and transferrin. Infect. Immunol. 56, 2774–2781.

    Google Scholar 

  • Engelmayer, J., Blezinger, P. and Varadhachary, A. (2008). Talactoferrin stimulates wound healing with modulation of inflammation. J. Surg. Res. 149, 278–286.

    Google Scholar 

  • Erdei, J., Forsgren, A. and Naidu, A.S. (1994). Lactoferrin binds to porins OmpF and OmpC in Escherichia coli. Infect. Immun. 62, 1236–1240.

    Google Scholar 

  • Fairweather-Tait, S.J., Balmer, S.E., Scott, P.H. and Minski, M.J. (1987). Lactoferrin and iron absorption in newborn infants. Pediatr. Res. 22, 651–654.

    Google Scholar 

  • Fernandez-Real, J.M., Garcia-Fuentes, E., Moreno-Navarrete, J.M., Murri-Pierri, M., Garrido-Sanchez, L., Ricart, W. and Tinahones, F. (2010). Fat overload induces changes in circulating lactoferrin that are associated with postprandial lipemia and oxidative stress in severely obese subjects. Obesity (Silver Spring) 18(3), 482–488.

    Google Scholar 

  • Fransson, G.B. and Lönnerdal, B. (1980). Iron in human milk. J. Pediatr. 96, 380–384.

    Google Scholar 

  • Fransson, G.B., Keen, C.L. and Lönnerdal, B. (1983). Supplementation of milk with iron bound to lactoferrin using weanling mice: L. Effects on hematology and tissue iron. J. Pediatr. Gastroenterol. Nutr. 2, 693–700.

    Google Scholar 

  • Fujihara, T., Nagano, T., Endo, K., Nakamura, M. and Nakata, K. (2000). Lactoferrin protects against UV-B irradiation-induced corneal epithelial damage in rats. Cornea 19, 207–211.

    Google Scholar 

  • Fujita, K., Ohnishi, T., Sekine, K., Iigo, M. and Tsuda, H. (2002). Down-regulation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced CYP1A2 expression is associated with bovine lactoferrin inhibition of MeIQx-induced liver and colon carcinogenesis in rats. Jpn. J. Cancer Res. 93, 616–625.

    Google Scholar 

  • Fujita, K., Matsuda, E., Sekine, K., Iigo, M. and Tsuda, H. (2004a). Lactoferrin enhances Fas expression and apoptosis in the colon mucosa of azoxymethane-treated rats. Carcinogenesis 25, 1961–1966.

    Google Scholar 

  • Fujita, K., Matsuda, E., Sekine, K., Iigo, M. and Tsuda, H. (2004b). Lactoferrin modifies apoptosis-related gene expression in the colon of the azoxymethane-treated rat. Cancer Lett. 213, 21–29.

    Google Scholar 

  • Gislason, J., Iyer, S., Hutchens, T.W. and Lönnerdal, B. (1993). Lactoferrin receptors in piglet small intestine: binding kinetics, specificity, ontogeny and regional distribution. J. Nutr. Biochem. 4, 528–533.

    Google Scholar 

  • Gomez, H.F., Ochoa, T.J., Carlin, L.G. and Cleary, T.G. (2003). Human lactoferrin impairs virulence of Shigella flexneri. J. Infect. Dis. 187, 87–95.

    Google Scholar 

  • Goodman, R.E. and Schanbacher, F.L. (1991). Bovine lactoferrin mRNA: sequence, analysis, and expression in the mammary gland. Biochem. Biophys. Res. Commun. 180, 75–84.

    Google Scholar 

  • Green, M.R. and Pastewka, J.V. (1978). Lactoferrin is a marker for prolactin response in mouse mammary explants. Endocrinology 103, 151–203.

    Google Scholar 

  • Griffiths, C.E., Cumberbatch, M., Tucker, S.C., Dearman, R.J., Andrew, S., Headon, D.R. and Kimber, I. (2001). Exogenous topical lactoferrin inhibits allergen-induced Langerhans cell migration and cutaneous inflammation in humans. Br. J. Dermatol. 144, 715–725.

    Google Scholar 

  • Grover, M., Giouzeppos, O., Schnagl, R.D. and May, J.T. (1997). Effect of human milk prostaglandins and lactoferrin on respiratory syncytial virus and rotavirus. Acta Paediatr. 86, 315–316.

    Google Scholar 

  • Guillen, C., McInnes, I.B., Vaughan, D., Speekenbrink, A.B. and Brock, J.H. (2000). The effects of local administration of lactoferrin on inflammation in murine autoimmune and infectious arthritis. Arthritis Rheum. 43, 2073–2080.

    Google Scholar 

  • Guillen, C., McInnes, I.B., Vaughan, D.M., Kommajosyula, S., Van Berkel, P.H., Leung, B.P., Aguila, A. and Brock, J. (2002). Enhanced Th1 response to Staphylococcus aureus infection in human lactoferrin-transgenic mice. J. Immunol. 168, 3950–3957.

    Google Scholar 

  • Guo, H.Y., Jiang, L., Ibrahim, S.A., Zhang, L., Zhang, H., Zhang, M. and Ren, F.Z. (2009). Orally administered lactoferrin preserves bone mass and microarchitecture in ovariectomized rats. J. Nutr. 139, 958–964.

    Google Scholar 

  • Hagiwara, T., Shinoda, I., Fukuwatari, Y. and Shimamura, S. (1995). Effects of lactoferrin and its peptides on proliferation of rat intestinal epithelial cell line, IEC-18, in the presence of epidermal growth factor. Biosci. Biotechnol. Biochem. 59, 1875–1881.

    Google Scholar 

  • Hara, K., Ikeda, M., Saito, S., Matsumoto, S., Numata, K., Kato, N., Tanaka, K. and Sekihara, H. (2002). Lactoferrin inhibits hepatitis B virus infection in cultured human hepatocytes. Hepatol. Res. 24, 228.

    Google Scholar 

  • Harada, E., Itoh, Y., Sitizyo, K., Takeuchi, T., Araki, Y. and Kitagawa, H. (1999). Characteristic transport of lactoferrin from the intestinal lumen into the bile via the blood in piglets. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 124, 321–327.

    Google Scholar 

  • Harmsen, M.C., Swart, P.J., de Bethune, M.P., Pauwels, R., De Clercq, E., The, T.H. and Meijer, D.K. (1995). Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J. Infect. Dis. 172, 380–388.

    Google Scholar 

  • Hasegawa, K., Motsuchi, W., Tanaka, S. and Dosako, S. (1994). Inhibition with lactoferrin of in vitro infection with human herpes virus. Jpn. J. Med. Sci. Biol. 47, 73–85.

    Google Scholar 

  • Hayes, T.G., Falchook, G.S. and Varadhachary, A. (2010). Phase IB trial of oral talactoferrin in the treatment of patients with metastatic solid tumors. Invest. New Drugs 28, 156–162.

    Google Scholar 

  • Heird, W.C., Schwarz, S.M. and Hansen, I.H. (1984). Colostrum-induced enteric mucosal growth in beagle puppies. Pediatr. Res. 18, 512–515.

    Google Scholar 

  • Hendrixson, D.R., Qiu, J., Shewry, S.C., Fink, D.L., Petty, S., Baker, E.N., Plaut, A.G. and St Geme, J.W., 3rd (2003). Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol. Microbiol. 47, 607–617.

    Google Scholar 

  • Hirashima, N., Orito, E., Ohba, K., Kondo, H., Sakamoto, T., Matsunaga, S., Kato, A., Nukaya, H., Sakakibara, K., Ohno, T., Kato, H., Sugauchi, F., Kato, T., Tanaka, Y., Ueda, R. and Mizokami, M. (2004). A randomized controlled trial of consensus interferon with or without lactoferrin for chronic hepatitis C patients with genotype 1b and high viral load. Hepatol. Res. 29, 9–12.

    Google Scholar 

  • Hu, W.L., Mazurier, J., Montreuil, J. and Spik, G. (1990). Isolation and partial characterization of a lactotransferrin receptor from mouse intestinal brush border. Biochemistry 29, 535–541.

    Google Scholar 

  • Hutchens, T.W., Henry, J.F., Yip, T.T., Hachey, D.L., Schanler, R.J., Motil, K.J. and Garza, C. (1991). Origin of intact lactoferrin and its DNA-binding fragments found in the urine of human milk-fed preterm infants. Evaluation by stable isotopic enrichment. Pediatr. Res. 29, 243–250.

    Google Scholar 

  • Iigo, M., Shimamura, M., Matsuda, E., Fujita, K., Nomoto, H., Satoh, J., Kojima, S., Alexander, D.B., Moore, M.A. and Tsuda, H. (2004). Orally administered bovine lactoferrin induces caspase-1 and interleukin-18 in the mouse intestinal mucosa: a possible explanation for inhibition of carcinogenesis and metastasis. Cytokine 25, 36–44.

    Google Scholar 

  • Iigo, M., Alexander, D.B., Long, N., Xu, J., Fukamachi, K., Futakuchi, M., Takase, M. and Tsuda, H. (2009). Anticarcinogenesis pathways activated by bovine lactoferrin in the murine small intestine. Biochimie 91, 86–101.

    Google Scholar 

  • Ishibashi, Y., Takeda, K., Tsukidate, N., Miyazaki, H., Ohira, K., Dosaka-Akita, H. and Nishimura, M. (2005). Randomized placebo-controlled trial of interferon alpha-2b plus ribavirin with and without lactoferrin for chronic hepatitis C. Hepatol. Res. 32, 218–223.

    Google Scholar 

  • Ishii, K., Takamura, N., Shinohara, M., Wakui, N., Shin, H., Sumino, Y., Ohmoto, Y., Teraguchi, S. and Yamauchi, K. (2003). Long-term follow-up of chronic hepatitis C patients treated with oral lactoferrin for 12 months. Hepatol. Res. 25, 226–233.

    Google Scholar 

  • Jiang, R., Lopez, V., Shannon, K.L. and Lönnerdal, B. (2011). Apo- and holo-lactoferrin are both internalized by lactoferrin receptor via clathrin-mediated endocytosis but differentially affect ERK-signaling and cell proliferation in Caco-2 cells. J. Cell. Physiol. 226, 3022–3031.

    Google Scholar 

  • Johansson, B.G. (1960). Isolation of an iron-containing red protein from human milk. Acta Chem. Scand. 14, 510–512.

    Google Scholar 

  • Jonasch, E., Stadler, W.M., Bukowski, R.M., Hayes, T.G., Varadhachary, A., Malik, R., Figlin, R.A. and Srinivas, S. (2008). Phase 2 trial of talactoferrin in previously treated patients with metastatic renal cell carcinoma. Cancer 113, 72–77.

    Google Scholar 

  • Kaito, M., Iwasa, M., Fujita, N., Kobayashi, Y., Kojima, Y., Ikoma, J., Imoto, I., Adachi, Y., Hamano, H. and Yamauchi, K. (2007). Effect of lactoferrin in patients with chronic hepatitis C: combination therapy with interferon and ribavirin. J. Gastroenterol. Hepatol. 22, 1894–1897.

    Google Scholar 

  • Kawakami, H. and Lönnerdal, B. (1991). Isolation and function of a receptor for human lactoferrin in human fetal intestinal brush-border membranes. Am. J. Physiol. 261, G841–G846.

    Google Scholar 

  • Kawakami, H., Hiratsuka, M. and Dosako, S. (1988). Effects of iron-saturated lactoferrin on iron absorption. Agric. Biol. Chem. 52, 903–908.

    Google Scholar 

  • Kimber, I., Cumberbatch, M., Dearman, R.J., Headon, D.R., Bhushan, M. and Griffiths, C.E. (2002). Lactoferrin: influences on Langerhans cells, epidermal cytokines, and cutaneous inflammation. Biochem. Cell Biol. 80, 103–107.

    Google Scholar 

  • King, J.C., Jr., Cummings, G.E., Guo, N., Trivedi, L., Readmond, B.X., Keane, V., Feigelman, S. and de Waard, R. (2007). A double-blind, placebo-controlled, pilot study of bovine lactoferrin supplementation in bottle-fed infants. J. Pediatr. Gastroenterol. Nutr. 44, 245–251.

    Google Scholar 

  • Krimpenfort, P. (1993). The production of human lactoferrin in the milk of transgenic animals. Cancer Detect. Prev. 17, 301–305.

    Google Scholar 

  • Kruzel, M.L., Bacsi, A., Choudhury, B., Sur, S. and Boldogh, I. (2006). Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma. Immunology 119, 159–166.

    Google Scholar 

  • Kruzel, M.L., Harari, Y., Mailman, D., Actor, J.K. and Zimecki, M. (2002). Differential effects of prophylactic, concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice. Clin. Exp. Immunol. 130, 25–31.

    Google Scholar 

  • Kuipers, M.E., de Vries, H.G., Eikelboom, M.C., Meijer, D.K. and Swart, P.J. (1999). Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates. Antimicrob. Agents Chemother. 43, 2635–2641.

    Google Scholar 

  • Kuwata, H., Yip, T.T., Tomita, M. and Hutchens, T.W. (1998). Direct evidence of the generation in human stomach of an antimicrobial peptide domain (lactoferricin) from ingested lactoferrin. Biochim. Biophys. Acta 1429, 129–141.

    Google Scholar 

  • Lönnerdal, B. and Bryant, A. (2006). Absorption of iron from recombinant human lactoferrin in young US women. Am. J. Clin. Nutr. 83, 305–309.

    Google Scholar 

  • Lönnerdal, B. and Hernell, O. (1994). Iron, zinc, copper and selenium status of breast-fed infants and infants fed trace element fortified milk-based infant formula. Acta Paediatr. 83, 367–373.

    Google Scholar 

  • Lönnerdal, B., Keen, C.L. and Hurley, L.S. (1985). Manganese binding proteins in human and cow’s milk. Am. J. Clin. Nutr. 41, 550–559.

    Google Scholar 

  • Lönnerdal, B., Zavaleta, N., Kusunoki, L., Lanata, C.F., Peerson, J.M. and Brown, K.H. (1996). Effect of postpartum maternal infection on proteins and trace elements in colostrum and early milk. Acta Paediatr. 85, 537–542.

    Google Scholar 

  • Leitch, E.C. and Willcox, M.D. (1999). Elucidation of the antistaphylococcal action of lactoferrin and lysozyme. J. Med. Microbiol. 48, 867–871.

    Google Scholar 

  • Liang, Q. and Richardson, T. (1993). Expression and characterization of human lactoferrin in yeast Saccharomyces cerevisiae. J. Agric. Food Chem. 41, 1800–1807.

    Google Scholar 

  • Liao, Y. and Lönnerdal, B. (2009). miR-584 mediates post-transcriptional expression of lactoferrin receptor in Caco-2 cells and in mouse small intestine during the perinatal period. Int. J. Biochem. Cell Biol. 42, 1363–1369.

    Google Scholar 

  • Lin, T.Y., Chu, C. and Chiu, C.H. (2002). Lactoferrin inhibits enterovirus 71 infection of human embryonal rhabdomyosarcoma cells in vitro. J. Infect. Dis. 186, 1161–1164.

    Google Scholar 

  • Lopez, V., Suzuki, Y.A. and Lönnerdal, B. (2006). Ontogenic changes in lactoferrin receptor and DMT1 in mouse small intestine: implications for iron absorption during early life. Biochem. Cell Biol. 84, 337–344.

    Google Scholar 

  • Lyons, T.E., Miller, M.S., Serena, T., Sheehan, P., Lavery, L., Kirsner, R.S., Armstrong, D.G., Reese, A., Yankee, E.W. and Veves, A. (2007). Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study. Am. J. Surg. 193, 49–54.

    Google Scholar 

  • Machnicki, M., Zimecki, M. and Zagulski, T. (1993). Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6 in vivo. Int. J. Exp. Pathol. 74, 433–439.

    Google Scholar 

  • Masson, P.L. and Heremans, J.F. (1971). Lactoferrin in milk from different species. Comp. Biochem. Physiol. B 39, 119–129.

    Google Scholar 

  • Masuda, C., Wanibuchi, H., Sekine, K., Yano, Y., Otani, S., Kishimoto, T., Tsuda, H. and Fukushima, S. (2000). Chemopreventive effects of bovine lactoferrin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder carcinogenesis. Jpn. J. Cancer Res. 91, 582–588.

    Google Scholar 

  • Mata, L., Sanchez, L., Headon, D.R. and Calvo, M. (1998). Thermal denaturation of human lactoferrin and its effect on the ability to bind iron. J. Agric. Food Chem. 40, 3964–3970.

    Google Scholar 

  • Mazurier, J., Montreuil, J. and Spik, G. (1985). Visualization of lactotransferrin brush-border receptors by ligand-blotting. Biochim. Biophys. Acta 821, 453–460.

    Google Scholar 

  • Mazurier, J., Legrand, D., Hu, W.L., Montreuil, J. and Spik, G. (1989). Expression of human lactotransferrin receptors in phytohemagglutinin-stimulated human peripheral blood lymphocytes. Isolation of the receptors by antiligand-affinity chromatography. Eur. J. Biochem. 179, 481–487.

    Google Scholar 

  • Mead, P.E. and Tweedie, J.W. (1990). cDNA and protein sequence of bovine lactoferrin. Nucleic Acids Res. 18, 7167.

    Google Scholar 

  • Metz-Boutigue, M.H., Jolles, J., Mazurier, J., Schoentgen, F., Legrand, D., Spik, G., Montreuil, J. and Jolles, P. (1984). Human lactotransferrin: amino acid sequence and structural comparisons with other transferrins. Eur. J. Biochem. 145, 659–676.

    Google Scholar 

  • Mikogami, T., Heyman, M., Spik, G. and Desjeux, J. F. (1994). Apical-to-basolateral transepithelial transport of human lactoferrin in the intestinal cell line HT-29cl.19A. Am. J. Physiol. 267, G308–G315.

    Google Scholar 

  • Molenaar, A.J., Kuys, Y.M., Davis, S.R., Wilkins, R.J., Mead, P.E. and Tweedie, J.W. (1996). Elevation of lactoferrin gene expression in developing, ductal, resting, and regressing parenchymal epithelium of the ruminant mammary gland. J. Dairy Sci. 79, 1198–1208.

    Google Scholar 

  • Nandi, S., Suzuki, Y.A., Huang, J., Yalda, D., Pham, P., Wu, L., Bartley, G., Huang, N. and Lönnerdal, B. (2002). Expression of human lactoferrin in transgenic rice grains for the application in infant formula. Plant Sci. 163, 713–722.

    Google Scholar 

  • Naot, D., Grey, A., Reid, I.R. and Cornish, J. (2005). Lactoferrin—a novel bone growth factor. Clin. Med. Res. 3, 93–101.

    Google Scholar 

  • Nichols, B.L., McKee, K.S. and Huebers, H.A. (1990). Iron is not required in the lactoferrin stimulation of thymidine incorporation into the DNA of rat crypt enterocytes. Pediatr. Res. 27, 525–528.

    Google Scholar 

  • Norrby, K. (2004). Human apo-lactoferrin enhances angiogenesis mediated by vascular endothelial growth factor A in vivo. J. Vasc. Res. 41, 293–304.

    Google Scholar 

  • Norrby, K., Mattsby-Baltzer, I., Innocenti, M. and Tuneberg, S. (2001). Orally administered bovine lactoferrin systemically inhibits VEGF(165)-mediated angiogenesis in the rat. Int. J. Cancer 91, 236–240.

    Google Scholar 

  • Nozaki, A., Ikeda, M., Naganuma, A., Nakamura, T., Inudoh, M., Tanaka, K. and Kato, N. (2003). Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein. J. Biol. Chem. 278, 10162–10173.

    Google Scholar 

  • Oguchi, S., Walker, W.A. and Sanderson, I.R. (1995). Iron saturation alters the effect of lactoferrin on the proliferation and differentiation of human enterocytes (Caco-2 cells). Biol. Neonate 67, 330–339.

    Google Scholar 

  • Oh, S.M., Hahm, D.H., Kim, I.H. and Choi, S.Y. (2001). Human neutrophil lactoferrin trans-activates the matrix metalloproteinase 1 gene through stress-activated MAPK signaling modules. J. Biol. Chem. 276, 42575–42579.

    Google Scholar 

  • Ono, T., Morishita, S., Fujisaki, C., Ohdera, M., Murakoshi, M., Iida, N., Kato, H., Miyashita, K., Iigo, M., Yoshida, T., Sugiyama, K. and Nishino, H. (2011). Effects of pepsin and trypsin on the anti-adipogenic action of lactoferrin against pre-adipocytes derived from rat mesenteric fat. Br. J. Nutr. 105, 200–211.

    Google Scholar 

  • Ono, T., Murakoshi, M., Suzuki, N., Iida, N., Ohdera, M., Iigo, M., Yoshida, T., Sugiyama, K. and Nishino, H. (2010). Potent anti-obesity effect of enteric-coated lactoferrin: decrease in visceral fat accumulation in Japanese men and women with abdominal obesity after 8-week administration of enteric-coated lactoferrin tablets. Br. J. Nutr. 104, 1688–1695.

    Google Scholar 

  • Pattamatta, U., Willcox, M., Stapleton, F., Cole, N. and Garrett, Q. (2009). Bovine lactoferrin stimulates human corneal epithelial alkali wound healing in vitro. Invest. Ophthalmol. Vis. Sci. 50, 1636–1643.

    Google Scholar 

  • Petschow, B.W., Talbott, R.D. and Batema, R.P. (1999). Ability of lactoferrin to promote the growth of Bifidobacterium spp. in vitro is independent of receptor binding capacity and iron saturation level. J. Med. Microbiol. 48, 541–549.

    Google Scholar 

  • Puddu, P., Borghi, P., Gessani, S., Valenti, P., Belardelli, F. and Seganti, L. (1998). Antiviral effect of bovine lactoferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection. Int. J. Biochem. Cell Biol. 30, 1055–1062.

    Google Scholar 

  • Qiu, J., Hendrixson, D.R., Baker, E.N., Murphy, T.F., St Geme, J.W., 3rd and Plaut, A.G. (1998). Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae. Proc. Natl. Acad. Sci. U.S.A. 95, 12641–12646.

    Google Scholar 

  • Rainard, P. (1986). Bacteriostatic activity of bovine milk lactoferrin against mastitic bacteria. Vet. Microbiol. 11, 387–392.

    Google Scholar 

  • Rejman, J.J., Oliver, S.P., Muenchen, R.A. and Turner, J.D. (1992). Proliferation of the MAC-T bovine mammary epithelial cell line in the presence of mammary secretion whey proteins. Cell Biol. Int. Rep. 16, 993–1001.

    Google Scholar 

  • Rey, M.W., Woloshuk, S.L., deBoer, H.A. and Pieper, F. R. (1990). Complete nucleotide sequence of human mammary gland lactoferrin. Nucleic Acids Res. 18, 5288.

    Google Scholar 

  • Roberts, A.K., Chierici, R., Sawatzki, G., Hill, M.J., Volpato, S. and Vigi, V. (1992). Supplementation of an adapted formula with bovine lactoferrin: 1. Effect on the infant faecal flora. Acta Paediatr. 81, 119–124.

    Google Scholar 

  • Saarinen, U.M. and Siimes, M.A. (1977). Iron absorption from infant milk formula and the optimal level of iron supplementation. Acta Paediatr. Scand. 66, 719–722.

    Google Scholar 

  • Saarinen, U.M., Siimes, M.A. and Dallman, P.R. (1977). Iron absorption in infants: high bioavailability of breast milk iron as indicated by the extrinsic tag method of iron absorption and by the concentration of serum ferritin. J. Pediatr. 91, 36–39.

    Google Scholar 

  • Saito, H., Miyakawa, H., Tamura, Y., Shimamura, S. and Tomita, M. (1991). Potent bactericidal activity of bovine lactoferrin hydrolysate produced by heat treatment at acidic pH. J. Dairy Sci. 74, 3724–3730.

    Google Scholar 

  • Salmon, V., Legrand, D., Georges, B., Slomianny, M.C., Coddeville, B. and Spik, G. (1997). Characterization of human lactoferrin produced in the baculovirus expression system. Protein Expr. Purif. 9, 203–210.

    Google Scholar 

  • Salmon, V., Legrand, D., Slomianny, M.C., El Yazidi, I., Spik, G., Gruber, V., Bournat, P., Olagnier, B., Mison, D., Theisen, M. and Merot, B. (1998). Production of human lactoferrin in transgenic tobacco plants. Protein Expr. Purif. 13, 127–135.

    Google Scholar 

  • Sawatzki, G. and Rich, I.N. (1989). Lactoferrin stimulates colony stimulating factor production in vitro and in vivo. Blood Cells 15, 371–385.

    Google Scholar 

  • Schulz-Lell, G., Dörner, K., Oldigs, H.D., Sievers, E. and Schaub, J. (1991). Iron availability from an infant formula supplemented with bovine lactoferrin. Acta Paediatr. Scand. 80, 155–158.

    Google Scholar 

  • Scott, P.H. (1989). Plasma lactoferrin levels in newborn preterm infants: effect of infection. Ann. Clin. Biochem. 26 (Pt 5), 412–415.

    Google Scholar 

  • Sekine, K., Watanabe, E., Nakamura, J., Takasuka, N., Kim, D.J., Asamoto, M., Krutovskikh, V., Baba-Toriyama, H., Ota, T., Moore, M.A., Masuda, M., Sugimoto, H., Nishino, H., Kakizoe, T. and Tsuda, H. (1997). Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats. Jpn. J. Cancer Res. 88, 523–526.

    Google Scholar 

  • Shimamura, M., Yamamoto, Y., Ashino, H., Oikawa, T., Hazato, T., Tsuda, H. and Iigo, M. (2004). Bovine lactoferrin inhibits tumor-induced angiogenesis. Int. J. Cancer 111, 111–116.

    Google Scholar 

  • Shin, K., Yamauchi, K., Teraguchi, S., Hayasawa, H., Tomita, M., Otsuka, Y. and Yamazaki, S. (1998). Antibacterial activity of bovine lactoferrin and its peptides against enterohaemorrhagic Escherichia coli O157:H7. Lett. Appl. Microbiol. 26, 407–411.

    Google Scholar 

  • Siimes, M. A., Salmenperä, L. and Perheentupa, J. (1984). Exclusive breast-feeding for 9 months: risk of iron deficiency. J. Pediatr. 104, 196–199.

    Google Scholar 

  • Singh, P.K., Gutmann, D.H., Fuller, C.E., Newsham, I.F. and Perry, A. (2002a). Differential involvement of protein 4.1 family members DAL-1 and NF2 in intracranial and intraspinal ependymomas. Mod. Pathol. 15, 526-531.

    Google Scholar 

  • Singh, P.K., Parsek, M.R., Greenberg, E.P. and Welsh, M.J. (2002). A component of innate immunity prevents bacterial biofilm development. Nature 417, 552–555.

    Google Scholar 

  • Slater, K. and Fletcher, J. (1987). Lactoferrin derived from neutrophils inhibits the mixed lymphocyte reaction. Blood 69, 1328–1333.

    Google Scholar 

  • Sørensen, M. and Sørensen, S.P.L. (1939). The protein in whey. C. R. Trav. Lab. Carlsberg 23, 55–99.

    Google Scholar 

  • Spik, G., Brunet, B., Mazurier-Dehaine, C., Fontaine, G. and Montreuil, J. (1982). Characterization and properties of the human and bovine lactotransferrins extracted from the faeces of newborn infants. Acta Paediatr. Scand. 71, 979–985.

    Google Scholar 

  • Spik, G., Coddeville, B. and Montreuil, J. (1988). Comparative study of the primary structures of sero-, lacto- and ovotransferrin glycans from different species. Biochimie 70, 1459–1469.

    Google Scholar 

  • Stowell, K.M., Rado, T.A., Funk, W.D. and Tweedie, J.W. (1991). Expression of cloned human lactoferrin in baby-hamster kidney cells. Biochem. J. 276 (Pt 2), 349–355.

    Google Scholar 

  • Sun, X.L., Baker, H.M., Shewry, S.C., Jameson, G.B. and Baker, E.N. (1999). Structure of recombinant human lactoferrin expressed in Aspergillus awamori. Acta Crystallogr. D Biol. Crystallogr. 55, 403–407.

    Google Scholar 

  • Superti, F., Ammendolia, M.G., Valenti, P. and Seganti, L. (1997). Antirotaviral activity of milk proteins: lactoferrin prevents rotavirus infection in the enterocyte-like cell line HT-29. Med. Microbiol Immunol. 186, 83–91.

    Google Scholar 

  • Superti, F., Siciliano, R., Rega, B., Giansanti, F., Valenti, P. and Antonini, G. (2001). Involvement of bovine lactoferrin metal saturation, sialic acid and protein fragments in the inhibition of rotavirus infection. Biochim. Biophys. Acta 1528, 107–115.

    Google Scholar 

  • Suzuki, Y.A., Shin, K. and Lönnerdal, B. (2001). Molecular cloning and functional expression of a human intestinal lactoferrin receptor. Biochemistry, 40, 15771–15779.

    Google Scholar 

  • Suzuki, Y.A., Kelleher, S.L., Yalda, D., Wu, L., Huang, J., Huang, N. and Lönnerdal, B. (2003). Expression, characterization, and biologic activity of recombinant human lactoferrin in rice. J. Pediatr. Gastroenterol. Nutr. 36, 190–199.

    Google Scholar 

  • Suzuki, Y.A., Wong, H., Ashida, K.Y., Schryvers, A.B. and Lönnerdal, B. (2008). The N1 domain of human lactoferrin is required for internalization by Caco-2 cells and targeting to the nucleus. Biochemistry 47, 10915–10920.

    Google Scholar 

  • Swart, P.J., Kuipers, M.E., Smit, C., Pauwels, R., de Bethune, M.P., de Clercq, E., Meijer, D.K. and Huisman, J.G. (1996). Antiviral effects of milk proteins: acylation results in polyanionic compounds with potent activity against human immunodeficiency virus types 1 and 2 in vitro. AIDS Res. Hum. Retroviruses 12, 769–775.

    Google Scholar 

  • Takayama, Y. and Mizumachi, K. (2001). Effects of lactoferrin on collagen gel contractile activity and myosin light chain phosphorylation in human fibroblasts. FEBS Lett. 508, 111–116.

    Google Scholar 

  • Tanaka, T., Kawabata, K., Kohno, H., Honjo, S., Murakami, M., Ota, T. and Tsuda, H. (2000). Chemopreventive effect of bovine lactoferrin on 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Jpn. J. Cancer Res. 91, 25–33.

    Google Scholar 

  • Tang, Z., Yin, Y., Zhang, Y., Huang, R., Sun, Z., Li, T., Chu, W., Kong, X., Li, L., Geng, M. and Tu, Q. (2009). Effects of dietary supplementation with an expressed fusion peptide bovine lactoferricin-lactoferrampin on performance, immune function and intestinal mucosal morphology in piglets weaned at age 21 d. Br. J. Nutr. 101, 998–1005.

    Google Scholar 

  • Teng, C.T., Pentecost, B.T., Chen, Y.H., Newbold, R.R., Eddy, E.M. and McLachlan, J.A. (1989). Lactotransferrin gene expression in the mouse uterus and mammary gland. Endocrinology 124, 992–999.

    Google Scholar 

  • Troost, F.J., Steijns, J., Saris, W.H. and Brummer, R.J. (2001). Gastric digestion of bovine lactoferrin in vivo in adults. J. Nutr. 131, 2101–2104.

    Google Scholar 

  • Troost, F.J., Saris, W.H. and Brummer, R.J. (2002). Orally ingested human lactoferrin is digested and secreted in the upper gastrointestinal tract in vivo in women with ileostomies. J. Nutr. 132, 2597–2600.

    Google Scholar 

  • Tsuda, H., Sekine, K., Fujita, K. and Ligo, M. (2002). Cancer prevention by bovine lactoferrin and underlying mechanisms—a review of experimental and clinical studies. Biochem. Cell Biol. 80, 131–136.

    Google Scholar 

  • Ueno, H., Sato, T., Yamamoto, S., Tanaka, K., Ohkawa, S., Takagi, H., Yokosuka, O., Furuse, J., Saito, H., Sawaki, A., Kasugai, H., Osaki, Y., Fujiyama, S., Sato, K., Wakabayashi, K. and Okusaka, T. (2006). Randomized, double-blind, placebo-controlled trial of bovine lactoferrin in patients with chronic hepatitis C. Cancer Sci. 97, 1105–1110.

    Google Scholar 

  • Ushida, Y., Sekine, K., Kuhara, T., Takasuka, N., Iigo, M., Maeda, M. and Tsuda, H. (1999). Possible chemopreventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat. Jpn. J. Cancer Res. 90, 262–267.

    Google Scholar 

  • van der Kraan, M.I., Groenink, J., Nazmi, K., Veerman, E.C., Bolscher, J.G. and Amerongen, A.V.N. (2004). Lactoferrampin: a novel antimicrobial peptide in the N1-domain of bovine lactoferrin. Peptides 25, 177–183.

    Google Scholar 

  • Van Snick, J.L. and Masson, P.L. (1976). The binding of human lactoferrin to mouse peritoneal cells. J. Exp. Med. 144, 1568-1580.

    Google Scholar 

  • Varadhachary, A., Wolf, J.S., Petrak, K., O’Malley, B.W., Jr., Spadaro, M., Curcio, C., Forni, G. and Pericle, F. (2004). Oral lactoferrin inhibits growth of established tumors and potentiates conventional chemotherapy. Int. J. Cancer 111, 398–403.

    Google Scholar 

  • Wakabayashi, H., Abe, S., Okutomi, T., Tansho, S., Kawase, K. and Yamaguchi, H. (1996). Cooperative anti-Candida effects of lactoferrin or its peptides in combination with azole antifungal agents. Microbiol. Immunol. 40, 821–825.

    Google Scholar 

  • Wang, W.P., Iigo, M., Sato, J., Sekine, K., Adachi, I. and Tsuda, H. (2000). Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin. Jpn. J. Cancer Res. 91, 1022–1027.

    Google Scholar 

  • Ward, P.P., May, G.S., Headon, D.R. and Conneely, O.M. (1992). An inducible expression system for the production of human lactoferrin in Aspergillus nidulans. Gene 122, 219–223.

    Google Scholar 

  • Ward, P.P., Piddington, C.S., Cunningham, G.A., Zhou, X., Wyatt, R.D. and Conneely, O.M. (1995). A system for production of commercial quantities of human lactoferrin: a broad spectrum natural antibiotic. Biotechnology (NY) 13, 498–503.

    Google Scholar 

  • Xiao, Y., Monitto, C.L., Minhas, K.M. and Sidransky, D. (2004). Lactoferrin down-regulates G1 cyclin-dependent kinases during growth arrest of head and neck cancer cells. Clin. Cancer Res. 10, 8683–8686.

    Google Scholar 

  • Yagi, M., Suzuki, N., Takayama, T., Arisue, M., Kodama, T., Yoda, Y., Numasaki, H., Otsuka, K. and Ito, K. (2008). Lactoferrin suppress the adipogenic differentiation of MC3T3-G2/PA6 cells. J. Oral Sci. 50, 419–425.

    Google Scholar 

  • Ye, X.Y., Wang, H.X., Liu, F. and Ng, T.B. (2000). Ribonuclease, cell-free translation-inhibitory and superoxide radical scavenging activities of the iron-binding protein lactoferrin from bovine milk. Int. J. Biochem. Cell Biol. 32, 235–241.

    Google Scholar 

  • Yi, M., Kaneko, S., Yu, D.Y. and Murakami, S. (1997). Hepatitis C virus envelope proteins bind lactoferrin. J. Virol. 71, 5997–6002.

    Google Scholar 

  • Zavaleta, N., Lanata, C., Butron, B., Peerson, J.M., Brown, K.H. and Lönnerdal, B. (1995a). Effect of acute maternal infection on quantity and composition of breast milk. Am. J. Clin. Nutr. 62, 559–563.

    Google Scholar 

  • Zavaleta, N., Nombera, J., Rojas, R., Hambraeus, L., Gislason, J. and Lönnerdal, B. (1995b). Iron and lactoferrin in milk of anemic mothers given iron supplements. Nutr. Res. 15, 681–690.

    Google Scholar 

  • Zavaleta, N., Figueroa, D., Rivera, J., Sanchez, J., Alfaro, S. and Lönnerdal, B. (2007). Efficacy of rice-based oral rehydration solution containing recombinant human lactoferrin and lysozyme in Peruvian children with acute diarrhea. J. Pediatr. Gastroenterol. Nutr. 44, 258–264.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutrition, University of California, Davis, CA, 95616, USA

    B. Lönnerdal

  2. Biochemical Laboratory, Saraya Co. Ltd., 24-12 Tamate-cho, Kashiwara-shi, Osaka, 582-0028, Japan

    Y. A. Suzuki

Authors
  1. B. Lönnerdal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. A. Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. Lönnerdal .

Editor information

Editors and Affiliations

  1. School of Food and Nutritional Sciences, University College Cork, Cork, College Ro, Ireland

    Paul L. H. McSweeney

  2. Fac. Food Technology & Nutrition, Dept. Food Science, University College Cork, Cork, Ireland

    Patrick F. Fox

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Lönnerdal, B., Suzuki, Y.A. (2013). Lactoferrin. In: McSweeney, P., Fox, P. (eds) Advanced Dairy Chemistry. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4714-6_10

Download citation

Publish with us

Policies and ethics

Search

Navigation