Lactoferrin

Advanced Dairy Chemistry: Volume 1A: Proteins: Basic Aspects, 4th Edition

Volumn , Issue , 2013, Pages 295-315

  Lonnerdal B ^a   Suzuki, Y A ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b SARAYA CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

IRON;

BIOLOGICAL FUNCTIONS; BOVINE LACTOFERRIN; COMMERCIAL APPLICATIONS; FOOD SUPPLEMENTS; HEALTH BENEFITS; IRON ABSORPTIONS; IRON-BINDING PROTEIN; LOW CONCENTRATIONS;

MAMMALS;

EID: 84948972064     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4614-4714-6_10     Document Type: Chapter

References (181)

1. Ainscough, E.W., Brodie, A.M. and Plowman, J.E. (1979). The chromium, manganese, cobalt and copper complexes of human lactoferrin. Inorg. Chim. Acta33, 145-153.
2. 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 lacto-ferrin and xylitol. Int. J. Antimicrob. Agents33, 230-236.
3. 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 Vitro20, 543-548.
4. Andersen, J.H., Jenssen, H., Sandvik, K. and Gutteberg, TJ. (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.
5. 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 A resolution. J. Mol. Biol.209, 711-734.
6. 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.
7. 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.
8. 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.
9. Baker, E.N. and Lindley, P.F. (1993). New perspectives on the structure and function of transferrins. J. Inorg. Biochem.47, 147-160.
10. 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.
11. Baveye, S., Elass, E., Fernig, D.G., Blanquart, C., Mazurier, J. and Legrand, D. (2000). Human lactofer- rin 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.
12. 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.
13. Bellamy, W., Takase, M., Yamauchi, K., Wakabayashi, H., Kawase, K. and Tomita, M. (1992). Identification of the bactericidal domain of lactoferrin. Biochim. Biophys. Acta1121, 130-136.
14. 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.
15. 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.
16. 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.
17. Bharadwaj, S., Naidu, A.G., Betageri, G.V., Prasadarao, N.V. and Naidu, A.S. (2009). Milk ribonuclease- enriched lactoferrin induces positive effects on boneturnover markers in postmenopausal women.Osteoporos. Int.20, 1603-1611.
18. 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.
19. 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.
20. Blakeborough, P., Salter, D.N. and Gurr, M.I. (1983). Zinc binding in cow’s milk and human milk. Biochem. J. 209, 505-512.
21. 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. Biochimie91, 123-132.
22. 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.
23. 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.
24. 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. Acta759, 229-235.
25. Brock, J.H. (1985). Lactoferrin in human milk: its role in iron absorption and protection against enteric infectionin the newborn infant. Arch. Dis. Child.55, 417-421.
26. Bullen, J.J., Rogers, H.J. and Leigh, L. (1972). Ironbinding proteins in milk and resistance to Escherichia coli infection in infants. Br. Med. J.1, 69-75.
27. 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.
28. Campbell, E.J. (1982). Human leukocyte elastase, cathep-sin G, and lactoferrin: family of neutrophil granule glycoproteins that bind to an alveolar macrophage receptor. Proc. Natl. Acad. Sci. USA.79, 6941-6945.
29. 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.
30. 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.
31. Cornish, J. (2004). Lactoferrin promotes bone growth. Biometals17, 331-335.
32. 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. Endocrinology145, 4366-4374.
33. Cox, T.M., Mazurier, J., Spik, G., Montreuil, J. and Peters, TJ. (1979). Iron binding proteins and influx of iron across the duodenal brush border. Evidence for specific lactotransferrin receptors in the human intestine. Biochim. Biophys. Acta588, 120-128.
34. Crouch, S.P., Slater, K.J. and Fletcher, J. (1992). Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood80, 235-240.
35. 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.
36. 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.
37. Davidson, L.A. and Lonnerdal, B. (1986). Isolation and characterization of rhesus monkey milk lactoferrin. Pediatr. Res.20, 197-201.
38. Davidson, L.A. and Lonnerdal, B. (1987). Persistence of human milk proteins in the breast-fed infant. Acta Paediatr. Scand.76, 733-740.
39. Davidson, L.A. and Lonnerdal, B. (1988). Specific binding of lactoferrin to brush-border membrane: ontogeny and effect of glycan chain. Am. J. Physiol.254, G580-G585.
40. Davidson, L.A. and Lonnerdal, 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.
41. Davidson, L.A., Litov, R.E. and Lonnerdal, B. (1990). Iron retention from lactoferrin-supplemented formulas in infant rhesus monkeys. Pediatr. Res.27, 176-180.
42. Davidsson, L., Kastenmayer, P., Yuen, M., Lonnerdal, B. and Hurrell, R.F. (1994). Influence of lactoferrin on iron absorption from human milk in infants. Pediatr. Res.35, 117-124.
43. Dionysius, D.A. and Milne, J.M. (1997). Antibacterial peptides of bovine lactoferrin: purification and characterization. J. Dairy Sci.80, 667-674.
44. Donovan, S.M., Atkinson, S.A., Whyte, R.K. and Lonnerdal, B. (1989). Partition of nitrogen intake and excretion in low-birth-weight infants. Am. J. Dis. Child.143, 1485-1491.
45. 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.
46. 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.
47. Ellison, R.T., 3rd and Giehl, TJ. (1991). Killing of Gramnegative bacteria by lactoferrin and lysozyme. J. Clin. Invest.88, 1080-1091.
48. Ellison, R.T., 3rd, Giehl, TJ. and LaForce, F.M. (1988). Damage of the outer membrane of enteric Gramnegative bacteria by lactoferrin and transferrin. Infect. Immunol.56, 2774-2781.
49. Engelmayer, J., Blezinger, P. and Varadhachary, A. (2008). Talactoferrin stimulates wound healing with modulation of inflammation. J. Surg. Res.149, 278-286.
50. Erdei, J., Forsgren, A. and Naidu, A.S. (1994). Lactoferrin binds to porins OmpF and OmpC inEscherichia coli. Infect. Immun.62, 1236-1240.
51. 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.
52. 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.
53. Fransson, G.B. and Lonnerdal, B. (1980). Iron in human milk. J. Pediatr.96, 380-384.
54. Fransson, G.B., Keen, C.L. and Lonnerdal, 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.
55. Fujihara, T., Nagano, T., Endo, K., Nakamura, M. and Nakata, K. (2000). Lactoferrin protects against UV-B irradiation-induced corneal epithelial damage in rats. Cornea19, 207-211.
56. Fujita, K., Ohnishi, T., Sekine, K., Iigo, M. and Tsuda, H. (2002). Down-regulation of 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MelQx)-induced CYP1A2 expression is associated with bovine lactoferrin inhibition of MelQx-induced liver and colon carcinogenesis in rats. Jpn. J. Cancer Res.93, 616-625.
57. 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. Carcinogenesis25, 1961-1966.
58. 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.
59. Gislason, J., Iyer, S., Hutchens, T.W. and Lonnerdal, B. (1993). Lactoferrin receptors in piglet small intestine: binding kinetics, specificity, ontogeny and regional distribution. J. Nutr. Biochem.4, 528-533.
60. 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.
61. 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.
62. Green, M.R. and Pastewka, J.V. (1978). Lactoferrin is a marker for prolactin response in mouse mammary explants. Endocrinology103, 151-203.
63. 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.
64. Grover, M., Giouzeppos, O., Schnagl, R.D. and May, J.T. (1997). Effect of human milk prostaglandins and lac-toferrin on respiratory syncytial virus and rotavirus. Acta Paediatr.86, 315-316.
65. 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.
66. Guillen, C., McInnes, I.B., Vaughan, D.M., Kommajosyula, K., 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.
67. 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.
68. 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.
69. 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.
70. 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.
71. Harmsen, M.C., Swart, PJ., de Bethune, M.P., Pauwels, R., De Clercq, E., The, T.H. and Meijer, D.K. (1995). Antiviral effects of plasma and milk proteins: lactofer- rin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replicationin vitro. J. Infect. Dis.172, 380-388.
72. 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.
73. 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 Drugs28, 156-162.
74. Heird, W.C., Schwarz, S.M. and Hansen, I.H. (1984). Colostrum-induced enteric mucosal growth in beagle puppies. Pediatr. Res.18, 512-515.
75. Hendrixson, D.R., Qiu, J., Shewry, S.C., Fink, D.L., Petty, k., 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.
76. 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.
77. Hu, W.L., Mazurier, J., Montreuil, J. and Spik, G. (1990). Isolation and partial characterization of a lactotrans- ferrin receptor from mouse intestinal brush border. Biochemistry29, 535-541.
78. 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.
79. 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. Cytokine25, 36-44.
80. 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. Biochimie91, 86-101.
81. 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 lacto- ferrin for chronic hepatitis C. Hepatol. Res.32, 218-223.
82. 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.
83. Jiang, R., Lopez, V, Shannon, K.L. and Lonnerdal, 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.
84. Johansson, B.G. (1960). Isolation of an iron-containing red protein from human milk. Acta Chem. Scand.14, 510-512.
85. 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. Cancer113, 72-77.
86. 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.
87. Kawakami, H. and Lonnerdal, B. (1991). Isolation and function of a receptor for human lactoferrin in human fetal intestinal brush-border membranes. Am. J. Physiol.261, G841-G846.
88. Kawakami, H., Hiratsuka, M. and Dosako, S. (1988). Effects of iron-saturated lactoferrin on iron absorption. Agric. Biol. Chem.52, 903-908.
89. 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.
90. 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.
91. Krimpenfort, P. (1993). The production of human lacto-ferrin in the milk of transgenic animals. Cancer Detect. Prev.17, 301-305.
92. 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. Immunology119, 159-166.
93. 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.
94. Kuipers, M.E., de Vries, H.G., Eikelboom, M.C., Meijer, D.K. and Swart, PJ. (1999). Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates. Antimicrob. Agents Chemother.43, 2635-2641.
95. 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 (lactofer- ricin) from ingested lactoferrin. Biochim. Biophys. Acta1429, 129-141.
96. Lonnerdal, B. and Bryant, A. (2006). Absorption of iron from recombinant human lactoferrin in young US women. Am. J. Clin. Nutr.83, 305-309.
97. Lonnerdal, 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.
98. Lonnerdal, 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.
99. Lonnerdal, 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.
100. Leitch, E.C. and Willcox, M.D. (1999). Elucidation of the antistaphylococcal action of lactoferrin and lysozyme. J. Med. Microbiol.48, 867-871.
101. Liang, Q. and Richardson, T. (1993). Expression and characterization of human lactoferrin in yeast Saccharomyces cerevisiae. J. Agric. Food Chem.41, 1800-1807.
102. Liao, Y. and Lonnerdal, 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.
103. Lin, T.Y., Chu, C. and Chiu, C.H. (2002). Lactoferrin inhibits enterovirus 71 infection of human embryonal rhabdomyosarcoma cells invitro. J. Infect. Dis.186, 1161-1164.
104. Lopez, V., Suzuki, Y.A. and Lonnerdal, 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.
105. 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.
106. Machnicki, M., Zimecki, M. and Zagulski, T. (1993). Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6in vivo. Int. J. Exp. Pathol.74, 433-439.
107. Masson, P.L. and Heremans, J.F. (1971). Lactoferrin in milk from different species. Comp. Biochem. Physiol. B39, 119-129.
108. 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.
109. 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.
110. Mazurier, J., Montreuil, J. and Spik, G. (1985). Visualization of lactotransferrin brush-border receptors by ligand-blotting. Biochim. Biophys. Acta821, 453-460.
111. 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.
112. Mead, P.E. and Tweedie, J.W. (1990). cDNA and protein sequence of bovine lactoferrin. Nucleic Acids Res.18, 7167.
113. 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.
114. 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.
115. Molenaar, A.J., Kuys, Y.M., Davis, S.R., Wilkins, R.J., Mead, P.E. and Tweedie, J.W. (1996). Elevation of lac-toferrin gene expression in developing, ductal, resting, and regressing parenchymal epithelium of the ruminant mammary gland. J. Dairy Sci.79, 1198-1208.
116. Nandi, S., Suzuki, Y.A., Huang, J., Yalda, D., Pham, P., Wu, L., Bartley, G., Huang, N. and Lonnerdal, B. (2002). Expression of human lactoferrin in transgenic rice grains for the application in infant formula. Plant Sci.163, 713-722.
117. Naot, D., Grey, A., Reid, I.R. and Cornish, J. (2005). Lactoferrin a novel bone growth factor. Clin. Med. Res.3, 93 - 101.
118. 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.
119. Norrby, K. (2004). Human apo-lactoferrin enhances angiogenesis mediated by vascular endothelial growth factor A in vivo. J. Vasc. Res.41, 293-304.
120. Norrby, K., Mattsby-Baltzer, I., Innocenti, M. and Tuneberg, S. (2001). Orally administered bovine lac-toferrin systemically inhibits VEGF(165)-mediated angiogenesis in the rat. Int. J. Cancer91, 236-240.
121. 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.
122. 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. Neonate67, 330-339.
123. 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.
124. 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.
125. 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 lactofer- rin tablets. Br. J. Nutr.104, 1688-1695.
126. 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.
127. 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.
128. Puddu, P., Borghi, P., Gessani, S., Valenti, P., Belardelli, F. and Seganti, L. (1998). Antiviral effect of bovine lac-toferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection. Int. J. Biochem. Cell Biol.30, 1055-1062.
129. 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.
130. Rainard, P. (1986). Bacteriostatic activity of bovine milk lactoferrin against mastitic bacteria. Vet. Microbiol. 11, 387-392.
131. 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.
132. 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.
133. 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.
134. 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.
135. 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.
136. 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.
137. 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.
138. 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.
139. Sawatzki, G. and Rich, I.N. (1989). Lactoferrin stimulates colony stimulating factor production in vitro and in vivo. Blood Cells15, 371-385.
140. Schulz-Lell, G., Dorner, 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.
141. Scott, P.H. (1989). Plasma lactoferrin levels in newborn preterm infants: effect of infection. Ann. Clin. Biochem. 26 (Pt 5), 412-415.
142. 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.
143. Shimamura, M., Yamamoto, Y., Ashino, H., Oikawa, T., Hazato, T., Tsuda, H. and Iigo, M. (2004). Bovine lactoferrin inhibits tumor-induced angiogenesis. Int. J. Cancer111, 111-116.
144. 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.
145. Siimes, M. A., Salmenpera, L. and Perheentupa, J. (1984). Exclusive breast-feeding for 9 months: risk of iron deficiency. J. Pediatr.104, 196-199.
146. Singh, P.K., Parsek, M.R., Greenberg, E.P. and Welsh, M.J. (2002). A component of innate immunity prevents bacterial biofilm development. Nature417, 552-555.
147. Slater, K. and Fletcher, J. (1987). Lactoferrin derived from neutrophils inhibits the mixed lymphocyte reaction. Blood69, 1328-1333.
148. Sprensen, M. and Sprensen, S.P.L. (1939). The protein in whey. C. R. Trav. Lab. Carlsberg23, 55-99.
149. 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.
150. Spik, G., Coddeville, B. and Montreuil, J. (1988). Comparative study of the primary structures of sero-, lacto- and ovotransferrin glycans from different species. Biochimie70, 1459-1469.
151. 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.
152. 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.
153. Superti, F., Ammendolia, M.G., Valenti, P. and Seganti, L. (1997). Antirotaviral activity of milk proteins: lactofer- rin prevents rotavirus infection in the enterocyte-like cell line HT-29. Med. Microbiol Immunol.186, 83-91.
154. 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. Acta1528, 107-115.
155. Suzuki, Y.A., Shin, K. and Lonnerdal, B. (2001). Molecular cloning and functional expression of a human intestinal lactoferrin receptor. Biochemistry, 40, 15771-15779.
156. Suzuki, Y.A., Kelleher, S.L., Yalda, D., Wu, L., Huang, J., Huang, N. and Lonnerdal, B. (2003). Expression, characterization, and biologic activity of recombinant human lactoferrin in rice. J. Pediatr. Gastroenterol. Nutr.36, 190-199.
157. Suzuki, Y.A., Wong, H., Ashida, K.Y., Schryvers, A.B. and Lonnerdal, B. (2008). The N1 domain of human lactoferrin is required for internalization by Caco-2 cells and targeting to the nucleus. Biochemistry47, 10915-10920.
158. 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. Retroviruses12, 769-775.
159. Takayama, Y. and Mizumachi, K. (2001). Effects of lacto-ferrin on collagen gel contractile activity and myosin light chain phosphorylation in human fibroblasts. FEBS Lett.508, 111-116.
160. Tanaka, T., Kawabata, K., Kohno, H., Honjo, S., Murakami, M., Ota, T. and Tsuda, H. (2000). Chemopreventive effect of bovine lactoferrin on 4-nit- roquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Jpn. J. Cancer Res.91, 25-33.
161. 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.
162. 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. Endocrinology124, 992-999.
163. 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.
164. 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.
165. 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.
166. 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.
167. Ushida, Y., Sekine, K., Kuhara, T., Takasuka, N., Iigo, M., Maeda, M. and Tsuda, H. (1999). Possible chemopre-ventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat. Jpn. J. Cancer Res.90, 262-267.
168. 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. Peptides25, 177-183.
169. Van Snick, J.L. and Masson, P.L. (1976). The binding of human lactoferrin to mouse peritoneal cells. J. Exp. Med.144, 1568-1580.
170. 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. Cancer111, 398-403.
171. 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.
172. 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.
173. 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. Gene122, 219-223.
174. 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 lac- toferrin: a broad spectrum natural antibiotic. Biotechnology (NY)13, 498-503.
175. Xiao, Y., Monitto, C.L., Minhas, K.M. and Sidransky, D. (2004). Lactoferrin down-regulates G1 cyclin-depen- dent kinases during growth arrest of head and neck cancer cells. Clin. Cancer Res.10, 8683-8686.
176. 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.
177. 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 ironbinding protein lactoferrin from bovine milk. Int. J. Biochem. Cell Biol.32, 235-241.
178. Yi, M., Kaneko, S., Yu, D.Y. and Murakami, S. (1997). Hepatitis C virus envelope proteins bind lactoferrin. J. Virol.71, 5997-6002.
179. Zavaleta, N., Lanata, C., Butron, B., Peerson, J.M., Brown, K. H. and Lonnerdal, B. (1995a). Effect of acute maternal infection on quantity and composition of breast milk. Am. J. Clin. Nutr.62, 559-563.
180. Zavaleta, N., Nombera, J., Rojas, R., Hambraeus, L., Gislason, J. and Lonnerdal, B. (1995b). Iron and lacto- ferrin in milk of anemic mothers given iron supplements. Nutr. Res.15, 681-690.
181. Zavaleta, N., Figueroa, D., Rivera, J., Sanchez, J., Alfaro, S. and Lonnerdal, 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.