Skip to main content
SpringerLink
Log in
Book cover

Bioactive Components of Milk pp 163–194Cite as

Lactoferrin Structure and Functions

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 606))

Abstract

Lactoferrin (Lf) is an iron binding glycoprotein of the transferrin family that is expressed in most biological fluids and is a major component of mammals’ innate immune system. Its protective effect ranges from direct antimicrobial activities against a large panel of microorganisms, including bacteria, viruses, fungi, and parasites, to anti-inflammatory and anticancer activities. This plethora of activities is made possible by mechanisms of action implementing not only the capacity of Lf to bind iron but also interactions of Lf with molecular and cellular components of both host and pathogens. This chapter summarizes our current understanding of the Lf structure-function relationships that explain the roles of Lf in host defense.

This is a preview of subscription content, 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   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anderson, B. F., Baker, H. M., Dodson, E. J., Norris, G. E., Rumball, S. V., Waters, J. M., & Baker, E. N. (1987). Structure of human lactoferrin at 3.2-Å resolution. Proceedings of the National Academy of Sciences USA, 84, 1769–1773.

    Article  CAS  Google Scholar 

  • Appelmelk, B. J., An, Y. Q., Geerts, M., Thijs, B. G., de Boer, H. A., MacLaren, D. M., de Graaff, J., & Nuijens, J. H. (1994). Lactoferrin is a lipid A-binding protein. Infection and Immunity, 62, 2628–2632.

    CAS  Google Scholar 

  • Baker, E. N., & Baker, H. M. (2005). Molecular structure, binding properties and dynamics of lactoferrin. Cellular and Molecular Life Sciences, 62, 2531–2539.

    Article  CAS  Google Scholar 

  • Baumrucker, C. R., Schanbacher, F., Shang, Y., & Green, M. H. (2006). Lactoferrin interaction with retinoid signaling: Cell growth and apoptosis in mammary cells. Domestic Animal Endocrinology, 30, 289–303.

    Article  CAS  Google Scholar 

  • Baveye, S., Elass, E., Fernig, D. G., Blanquart, C., Mazurier, J., & 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. Infection and Immunity, 68, 6519–6525.

    Article  CAS  Google Scholar 

  • Bellamy, W., Takase, M., Yamauchi, K., Wakabayashi, H., Kawase, K., & Tomita, M. (1992). Identification of the bactericidal domain of lactoferrin. Biochimica et Biophysica Acta, 1121, 130–136.

    CAS  Google Scholar 

  • Benaïssa, M., Peyrat, J. P., Hornez, L., Mariller, C., Mazurier, J., & Pierce, A. (2005). Expression and prognostic value of lactoferrin mRNA isoforms in human breast cancer. International Journal of Cancer, 114, 299–306.

    Article  CAS  Google Scholar 

  • Bezault, J., Bhimani, R., Wiprovnick, J., & Furmanski, P. (1994). Human lactoferrin inhibits growth of solid tumors and development of experimental metastases in mice. Cancer Research, 54, 2310–2312.

    CAS  Google Scholar 

  • Breton, M., Mariller, C., Benaïssa, M., Caillaux, K., Browaeys, E., Masson, M., Vilain, J. P., Mazurier, J., & Pierce, A. (2004). Expression of delta-lactoferrin induces cell cycle arrest. Biometals, 17, 325–329.

    Article  CAS  Google Scholar 

  • Britigan, B. E., Lewis, T. S., Waldschmidt, M., McCormick, M. L., & Krieg, A. M. (2001). Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells. Journal of Immunology, 167, 2921–2928.

    CAS  Google Scholar 

  • Buderus, S., Boone, J., Lyerly, D., & Lentze, M. J. (2004). Fecal lactoferrin: A new parameter to monitor infliximab therapy. Digestive Diseases and Sciences, 49, 1036–1039.

    Article  CAS  Google Scholar 

  • Callebaut, C., Blanco, J., Benkirane, N., Krust, B., Jacotot, E., Guichard, G., Seddiki, N., Svab, J., Dam, E., Muller, S., Briand, J. P., & Hovanessian, A. G. (1998). Identification of V3 loop-binding proteins as potential receptors implicated in the binding of HIV particles to CD4(+) cells. Journal of Biological Chemistry, 273, 21988–21997.

    Article  CAS  Google Scholar 

  • Chandra Mohan, K. V., Devaraj, H., Prathiba, D., Hara, Y., & Nagini, S. (2006a). Antiproliferative and apoptosis inducing effect of lactoferrin and black tea polyphenol combination on hamster buccal pouch carcinogenesis. Biochimica et Biophysica Acta, 1760, 1536–1544.

    CAS  Google Scholar 

  • Chandra Mohan, K. V., Kumaraguruparan, R., Prathiba, D., & Nagini, S. (2006b). Modulation of xenobiotic-metabolizing enzymes and redox status during chemoprevention of hamster buccal carcinogenesis by bovine lactoferrin. Nutrition, 22, 940–946.

    Article  CAS  Google Scholar 

  • Chodaczek, G., Zimecki, M., Lukasiewicz, J., & Lugowski, C. (2006). A complex of lactoferrin with monophosphoryl lipid A is an efficient adjuvant of the humoral and cellular immune response in mice. Medical Microbiology and Immunology, 195, 207–216.

    Article  CAS  Google Scholar 

  • Coddeville, B., Strecker, G., Wieruszeski, J. M., Vliegenthart, J. F., van Halbeek, H., Peter-Katalinic, J., Egge, H., & Spik, G. (1992). Heterogeneity of bovine lactotransferrin glycans. Characterization of α-D-Galp-(1–>3)-β-D-Gal- and α-NeuAc-(2–>6)-β-D-GalpNAc-(1–>4)-β-D-GlcNAc-substituted N-linked glycans. Carbohydrate Research, 236, 145–164.

    Article  CAS  Google Scholar 

  • Cornish, J., Palmano, K., Callon, K. E., Watson, M., Lin, J. M., Valenti, P., Naot, D., Grey, A. B., & Reid, I. R. (2006). Lactoferrin and bone; structure-activity relationships. Biochemistry and Cell Biology, 84, 297–302.

    Article  CAS  Google Scholar 

  • Cumberbatch, M., Bhushan, M., Dearman, R. J., Kimber, I., & Griffiths, C. E. (2003). IL-1β-induced Langerhans' cell migration and TNF-α production in human skin: Regulation by lactoferrin. Clinical and Experimental Immunology, 132, 352–359.

    Article  CAS  Google Scholar 

  • Curran, C. S., Demick, K. P., & Mansfield, J. M. (2006). Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways. Cellular Immunology, 242, 23–30.

    Article  CAS  Google Scholar 

  • Damiens, E., El Yazidi, I., Mazurier, J., Elass-Rochard, E., Duthille, I., Spik, G., & Boilly-Marer, Y. (1998a). Role of heparan sulphate proteoglycans in the regulation of human lactoferrin binding and activity in the MDA-MB-231 breast cancer cell line. European Journal of Cell Biology, 77, 344–351.

    CAS  Google Scholar 

  • Damiens, E., Mazurier, J., El Yazidi, I., Masson, M., Duthille, I., Spik, G., & Boilly-Marer, Y. (1998b). Effects of human lactoferrin on NK cell cytotoxicity against haematopoietic and epithelial tumour cells. Biochimica et Biophysica Acta, 1402, 277–287.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Dhennin-Duthille, I., Masson, M., Damiens, E., Fillebeen, C., Spik, G., & Mazurier, J. (2000). Lactoferrin upregulates the expression of CD4 antigen through the stimulation of the mitogen-activated protein kinase in the human lymphoblastic T Jurkat cell line. Journal of Cellular Biochemistry, 79, 583–593.

    Article  CAS  Google Scholar 

  • Di Biase, A. M., Pietrantoni, A., Tinari, A., Siciliano, R., Valenti, P., Antonini, G., Seganti, L., & Superti, F. (2003). Heparin-interacting sites of bovine lactoferrin are involved in anti-adenovirus activity. Journal of Medical Virology, 69, 495–502.

    Article  CAS  Google Scholar 

  • Di Biase, A. M., Tinari, A., Pietrantoni, A., Antonini, G., Valenti, P., Conte, M. P., & Superti, F. (2004). Effect of bovine lactoferricin on enteropathogenic Yersinia adhesion and invasion in HEp-2 cells. Journal of Medical Microbiology, 53, 407–412.

    Article  CAS  Google Scholar 

  • Dial, E. J., & Lichtenberger, L. M. (2002). Effect of lactoferrin on Helicobacter felis induced gastritis. Biochemistry and Cell Biology, 80, 113–117.

    Article  CAS  Google Scholar 

  • Dial, E. J., Dohrman, A. J., Romero, J. J., & Lichtenberger, L. M. (2005). Recombinant human lactoferrin prevents NSAID-induced intestinal bleeding in rodents. Journal of Pharmacy and Pharmacology, 57, 93–99.

    Article  CAS  Google Scholar 

  • Diarra, M. S., Petitclerc, D., Deschenes, E., Lessard, N., Grondin, G., Talbot, B. G., & Lacasse, P. (2003). Lactoferrin against Staphylococcus aureus mastitis. Lactoferrin alone or in combination with penicillin G on bovine polymorphonuclear function and mammary epithelial cells colonisation by Staphylococcus aureus. Veterinary Immunology and Immunopathology, 95, 33–42.

    Article  CAS  Google Scholar 

  • Dziadek, B., Dziadek, J., & Dlugonska, H. (2007). Identification of Toxoplasma gondii proteins binding human lactoferrin: A new aspect of rhoptry proteins function. Experimental Parasitology, 115, 277–282.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Elass-Rochard, E., Roseanu, A., Legrand, D., Trif, M., Salmon, V., Motas, C., Montreuil, J., & Spik, G. (1995). Lactoferrin-lipopolysaccharide interaction: Involvement of the 28-34 loop region of human lactoferrin in the high-affinity binding to Escherichia coli 055B5 lipopolysaccharide. Biochemical Journal, 312 (Pt 3), 839–845.

    CAS  Google Scholar 

  • Elass-Rochard, E., Legrand, D., Salmon, V., Roseanu, A., Trif, M., Tobias, P. S., Mazurier, J., & Spik, G. (1998). Lactoferrin inhibits the endotoxin interaction with CD14 by competition with the lipopolysaccharide-binding protein. Infection and Immunity, 66, 486–491.

    CAS  Google Scholar 

  • Ellison, R. T., III, LaForce, F. M., Giehl, T. J., Boose, D. S., & Dunn, B. E. (1990). Lactoferrin and transferrin damage of the Gram-negative outer membrane is modulated by Ca2+ and Mg2+. Journal of General Microbiology, 136, 1437–1446.

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Farley, J., Loup, D., Nelson, M., Mitchell, A., Esplund, G., Macri, C., Harrison, C., & Gray, K. (1997). Neoplastic transformation of the endocervix associated with downregulation of lactoferrin expression. Molecular Carcinogenesis, 20, 240–250.

    Article  CAS  Google Scholar 

  • Fillebeen, C., Descamps, L., Dehouck, M. P., Fenart, L., Benaïssa, M., Spik, G., Cecchelli, R., & Pierce, A. (1999). Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. Journal of Biological Chemistry, 274, 7011–7017.

    Article  CAS  Google Scholar 

  • Fischer, R., Debbabi, H., Dubarry, M., Boyaka, P., & Tomé, D. (2006). Regulation of physiological and pathological Th1 and Th2 responses by lactoferrin. Biochemistry and Cell Biology, 84, 303–311.

    Article  CAS  Google Scholar 

  • Fritsch, G., Sawatzki, G., Treumer, J., Jung, A., & Spira, D. T. (1987). Plasmodium falciparum: Inhibition in vitro with lactoferrin, desferriferrithiocin, and desferricrocin. Experimental Parasitology, 63, 1–9.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Gahr, M., Speer, C. P., Damerau, B., & Sawatzki, G. (1991). Influence of lactoferrin on the function of human polymorphonuclear leukocytes and monocytes. Journal of Leukocyte Biology, 49, 427–433.

    CAS  Google Scholar 

  • Gifford, J. L., Hunter, H. N., & Vogel, H. J. (2005). Lactoferricin: A lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties. Cellular and Molecular Life Sciences, 62, 2588–2598.

    Article  CAS  Google Scholar 

  • Goldman, A. S., Garza, C., Schanler, R. J., & Goldblum, R. M. (1990). Molecular forms of lactoferrin in stool and urine from infants fed human milk. Pediatric Research, 27, 252–255.

    Article  CAS  Google Scholar 

  • Gomez, H. F., Ochoa, T. J., Carlin, L. G., & Cleary, T. G. (2003). Human lactoferrin impairs virulence of Shigella flexneri. Journal of Infectious Diseases, 187, 87–95.

    Article  CAS  Google Scholar 

  • Greenberg, D. E., Jiang, Z. D., Steffen, R., Verenker, M. P., & DuPont, H. L. (2002). Markers of inflammation in bacterial diarrhea among travelers, with a focus on enteroaggregative Escherichia coli pathogenicity. Journal of Infectious Diseases, 185, 944–949.

    Article  Google Scholar 

  • Grey, A., Banovic, T., Zhu, Q., Watson, M., Callon, K., Palmano, K., Ross, J., Naot, D., Reid, I. R., & Cornish, J. (2004). The low-density lipoprotein receptor-related protein 1 is a mitogenic receptor for lactoferrin in osteoblastic cells. Molecular Endocrinology, 18, 2268–2278.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Groot, F., Geijtenbeek, T. B., Sanders, R. W., Baldwin, C. E., Sanchez-Hernandez, M., Floris, R., van Kooyk, Y., de Jong, E. C., & Berkhout, B. (2005). Lactoferrin prevents dendritic cell-mediated human immunodeficiency virus type 1 transmission by blocking the DC-SIGN–gp120 interaction. Journal of Virology, 79, 3009–3015.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Hasegawa, K., Motsuchi, W., Tanaka, S., & Dosako, S. (1994). Inhibition with lactoferrin of in vitro infection with human herpes virus. Japanese Journal of Medical Science and Biology, 47, 73–85.

    CAS  Google Scholar 

  • Haversen, L., Ohlsson, B. G., Hahn-Zoric, M., Hanson, L. A., & Mattsby-Baltzer, I. (2002). Lactoferrin down-regulates the LPS-induced cytokine production in monocytic cells via NF-κB. Cellular Immunology, 220, 83–95.

    Article  CAS  Google Scholar 

  • Hayashida, K., Kaneko, T., Takeuchi, T., Shimizu, H., Ando, K., & Harada, E. (2004). Oral administration of lactoferrin inhibits inflammation and nociception in rat adjuvant-induced arthritis. Journal of Veterinary Medical Science, 66, 149–154.

    Article  CAS  Google Scholar 

  • He, J., & Furmanski, P. (1995). Sequence specificity and transcriptional activation in the binding of lactoferrin to DNA. Nature, 373, 721–724.

    Article  CAS  Google Scholar 

  • He, S., McEuen, A. R., Blewett, S. A., Li, P., Buckley, M. G., Leufkens, P., & Walls, A. F. (2003). The inhibition of mast cell activation by neutrophil lactoferrin: Uptake by mast cells and interaction with tryptase, chymase and cathepsin G. Biochemical Pharmacology, 65, 1007–1015.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  • Herz, J., & Strickland, D. K. (2001). LRP: A multifunctional scavenger and signaling receptor. Journal of Clinical Investigation, 108, 779–784.

    Article  CAS  Google Scholar 

  • Hwang, S. A., Kruzel, M. L., & Actor, J. K. (2005). Lactoferrin augments BCG vaccine efficacy to generate T helper response and subsequent protection against challenge with virulent Mycobacterium tuberculosis. International Immunopharmacology, 5, 591–599.

    Article  CAS  Google Scholar 

  • Iigo, M., Kuhara, T., Ushida, Y., Sekine, K., Moore, M. A., & Tsuda, H. (1999). Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice. Clinical and Experimental Metastasis, 17, 35-40.

    CAS  Google Scholar 

  • Iigo, M., Shimamura, M., Matsuda, E., Fujita, K., Nomoto, H., Satoh, J., Kojima, S., Alexander, D. B., Moore, M. A., & 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.

    Article  CAS  Google Scholar 

  • Iijima, H., Tomizawa, Y., Iwasaki, Y., Sato, K., Sunaga, N., Dobashi, K., Saito, R., Nakajima, T., Minna, J. D., & Mori, M. (2006). Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers. International Journal of Cancer, 118, 797–801.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Jameson, G. B., Anderson, B. F., Norris, G. E., Thomas, D. H., & Baker, E. N. (1998). Structure of human apolactoferrin at 2.0 Å resolution. Refinement and analysis of ligand-induced conformational change. Acta Crystallographica D, 54, 1319–1335.

    CAS  Google Scholar 

  • Japelj, B., Pristovsek, P., Majerle, A., & Jerala, R. (2005). Structural origin of endotoxin neutralization and antimicrobial activity of a lactoferrin-based peptide. Journal of Biological Chemistry, 280, 16955–16961.

    Article  CAS  Google Scholar 

  • Kai, K., Komine, K., Komine, Y., Kuroishi, T., Kozutsumi, T., Kobayashi, J., Ohta, M., Kitamura, H., & Kumagai, K. (2002). Lactoferrin stimulates Staphylococcus aureus killing activity of bovine phagocytes in the mammary gland. Microbiology and Immunology, 46, 187–194.

    CAS  Google Scholar 

  • Kane, S. V., Sandborn, W. J., Rufo, P. A., Zholudev, A., Boone, J., Lyerly, D., Camilleri, M., & Hanauer, S. B. (2003). Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. American Journal of Gastroenterology, 98, 1309–1314.

    Article  CAS  Google Scholar 

  • Katunuma, N., Le, Q. T., Murata, E., Matsui, A., Majima, E., Ishimaru, N., Hayashi, Y., & Ohashi, A. (2006). A novel apoptosis cascade mediated by lysosomal lactoferrin and its participation in hepatocyte apoptosis induced by D-galactosamine. FEBS Letters, 580, 3699–3705.

    Article  CAS  Google Scholar 

  • Katunuma, N., Murata, E., Le, Q.T., Hayashi, Y., & Ohashi, A. (2004). New apoptosis cascade mediated by lysosomal enzyme and its protection by epigallo-catechin gallate. Advances in Enzyme Regulation, 44, 1–10.

    CAS  Google Scholar 

  • Kawasaki, Y., Tazume, S., Shimizu, K., Matsuzawa, H., Dosako, S., Isoda, H., Tsukiji, M., Fujimura, R., Muranaka, Y., & Isihida, H. (2000). Inhibitory effects of bovine lactoferrin on the adherence of enterotoxigenic Escherichia coli to host cells. Bioscience, Biotechnology, and Biochemistry, 64, 348–354.

    Article  CAS  Google Scholar 

  • Kim, C. W., Son, K. N., Choi, S. Y., & Kim, J. (2006). Human lactoferrin upregulates expression of KDR/Flk-1 and stimulates VEGF-A-mediated endothelial cell proliferation and migration. FEBS Letters, 580, 4332–4336.

    Article  CAS  Google Scholar 

  • Konishi, M., Iwasa, M., Yamauchi, K., Sugimoto, R., Fujita, N., Kobayashi, Y., Watanabe, S., Teraguchi, S., Adachi, Y., & Kaito, M. (2006). Lactoferrin inhibits lipid peroxidation in patients with chronic hepatitis C. Hepatology Research, 36, 27–32.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Kuhara, T., Iigo, M., Itoh, T., Ushida, Y., Sekine, K., Terada, N., Okamura, H., & Tsuda, H. (2000). Orally administered lactoferrin exerts an antimetastatic effect and enhances production of IL-18 in the intestinal epithelium. Nutrition and Cancer, 38, 192–199.

    Article  CAS  Google Scholar 

  • Kuhara, T., Yamauchi, K., Tamura, Y., & Okamura, H. (2006). Oral administration of lactoferrin increases NK cell activity in mice via increased production of IL-18 and type I IFN in the small intestine. Journal of Interferon Cytokine Research, 26, 489–499.

    Article  CAS  Google Scholar 

  • Kumar, J., Weber, W., Münchau, S., Yadav, S., Bhaskar Singh, S., Saravanan, K., Paramasivam, M., Sharma, S., Kaur, P., Bhushan, A., Srinivasan, A., Betzel, C., & Singh, T. P. (2003). Crystal structure of human seminal diferric lactoferrin at 3.4 Å resolution. Indian Journal of Biochemistry and Biophysics, 40, 14–21.

    CAS  Google Scholar 

  • Legrand, D., Mazurier, J., Metz-Boutigue, M. H., Jollès, J., Jollès, P., Montreuil, J., & Spik, G. (1984). Characterization and localization of an iron-binding 18-kDa glycopeptide isolated from the N-terminal half of human lactotransferrin. Biochimica et Biophysica Acta, 787, 90–96.

    CAS  Google Scholar 

  • Legrand, D., van Berkel, P. H., Salmon, V., van Veen, H. A., Slomianny, M. C., Nuijens, J. H., & Spik, G. (1997). The N-terminal Arg2, Arg3 and Arg4 of human lactoferrin interact with sulphated molecules but not with the receptor present on Jurkat human lymphoblastic T-cells. Biochemical Journal, 327 (Pt 3), 841–846.

    CAS  Google Scholar 

  • Legrand, D., Vigié, K., Said, E. A., Elass, E., Masson, M., Slomianny, M. C., Carpentier, M., Briand, J. P., Mazurier, J., & Hovanessian, A. G. (2004). Surface nucleolin participates in both the binding and endocytosis of lactoferrin in target cells. European Journal of Biochemistry, 271, 303–317.

    Article  CAS  Google Scholar 

  • Legrand, D., Elass, E., Carpentier, M., & Mazurier, J. (2005). Lactoferrin: A modulator of immune and inflammatory responses. Cellular and Molecular Life Sciences, 62, 2549–2559.

    Article  CAS  Google Scholar 

  • Li, Y. M., Tan, A. X., & Vlassara, H. (1995). Antibacterial activity of lysozyme and lactoferrin is inhibited by binding of advanced glycation-modified proteins to a conserved motif. Nature Medicine, 1, 1057–1061.

    Article  CAS  Google Scholar 

  • Lima, M. F., & Kierszenbaum, F. (1987). Lactoferrin effects on the interaction of blood forms of Trypanosoma cruzi with mononuclear phagocytes. International Journal for Parasitology, 17, 1205–1208.

    Article  CAS  Google Scholar 

  • Lin, T. Y., Chiou, S. H., Chen, M., & Kuo, C. D. (2005). Human lactoferrin exerts bi-directional actions on PC12 cell survival via ERK1/2 pathway. Biochemical and Biophysical Research Communications, 337, 330–336.

    Article  CAS  Google Scholar 

  • Ling, J. M., & Schryvers, A. B. (2006). Perspectives on interactions between lactoferrin and bacteria. Biochemistry and Cell Biology, 84, 275–281.

    Article  CAS  Google Scholar 

  • Liu, D., Wang, X., Zhang, Z., & Teng, C. T. (2003). An intronic alternative promoter of the human lactoferrin gene is activated by Ets. Biochemical and Biophysical Research Communications, 301, 472–479.

    Article  CAS  Google Scholar 

  • Longhi, C., Conte, M. P., Seganti, L., Polidoro, M., Alfsen, A., & Valenti, P. (1993). Influence of lactoferrin on the entry process of Escherichia coli HB101 (pRI203) in HeLa cells. Medical Microbiology and Immunology, 182, 25–35.

    Article  CAS  Google Scholar 

  • Lorget, F., Clough, J., Oliveira, M., Daury, M. C., Sabokbar, A., & Offord, E. (2002). Lactoferrin reduces in vitro osteoclast differentiation and resorbing activity. Biochemical and Biophysical Research Communications, 296, 261–266.

    Article  CAS  Google Scholar 

  • Mader, J. S., Salsman, J., Conrad, D. M., & Hoskin, D. W. (2005). Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines. Molecular Cancer Therapeutics, 4, 612–624.

    Article  CAS  Google Scholar 

  • Mann, D. M., Romm, E., & Migliorini, M. (1994). Delineation of the glycosaminoglycan-binding site in the human inflammatory response protein lactoferrin. Journal of Biological Chemistry, 269, 23661–23667.

    CAS  Google Scholar 

  • Marchetti, M., Longhi, C., Conte, M. P., Pisani, S., Valenti, P., & Seganti, L. (1996). Lactoferrin inhibits herpes simplex virus type 1 adsorption to Vero cells. Antiviral Research, 29, 221–231.

    Article  CAS  Google Scholar 

  • Mariller, C., Benaïssa, M., Hardivillé, S., Breton, M., Pradelle, G., Mazurier, J., & Pierce, A. (2007). Human delta-lactoferrin is a transcription factor which enhances Skp1 (S-phase kinase associated protein) gene expression. FEBS Journal, 274, 2038–2053.

    Article  CAS  Google Scholar 

  • Masson, P. L., Heremans, J. F., & Schonne, E. (1969). Lactoferrin, an iron-binding protein in neutrophilic leukocytes. Journal of Experimental Medicine, 130, 643–658.

    Article  CAS  Google Scholar 

  • Matsuda, Y., Saoo, K., Hosokawa, K., Yamakawa, K., Yokohira, M., Zeng, Y., Takeuchi, H., & Imaida, K. (2007). Post-initiation chemopreventive effects of dietary bovine lactoferrin on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in female A/J mice. Cancer Letters, 246, 41–46.

    Article  CAS  Google Scholar 

  • Mazurier, J., & Spik, G. (1980). Comparative study of the iron-binding properties of human transferrins. I. Complete and sequential iron saturation and desaturation of the lactotransferrin. Biochimica et Biophysica Acta, 629, 399–408.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • McAbee, D. D., Jiang, X., & Walsh, K. B. (2000). Lactoferrin binding to the rat asialoglycoprotein receptor requires the receptor's lectin properties. Biochemical Journal, 348 (Pt 1), 113–117.

    Article  CAS  Google Scholar 

  • Medina, I., Tombo, I., Satue-Gracia, M. T., German, J. B., & Frankel, E. N. (2002). Effects of natural phenolic compounds on the antioxidant activity of lactoferrin in liposomes and oil-in-water emulsions. Journal of Agricultural and Food Chemistry, 50, 2392–2399.

    Article  CAS  Google Scholar 

  • Meilinger, M., Haumer, M., Szakmary, K. A., Steinbock, F., Scheiber, B., Goldenberg, H., & Huettinger, M. (1995). Removal of lactoferrin from plasma is mediated by binding to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor and transport to endosomes. FEBS Letters, 360, 70–74.

    Article  CAS  Google Scholar 

  • Metz-Boutigue, M. H., Jollès, J., Mazurier, J., Schoentgen, F., Legrand, D., Spik, G., Montreuil, J., & Jollès, P. (1984). Human lactotransferrin: Amino acid sequence and structural comparisons with other transferrins. European Journal of Biochemistry, 145, 659–676.

    Article  CAS  Google Scholar 

  • Montreuil, J., Tonnelat, J., & Mullet, S. (1960). Preparation and properties of lactosiderophilin (lactotransferrin) of human milk. [in French] Biochimica et Biophysica Acta, 45, 413–421.

    Google Scholar 

  • Moshynskyy, I., Jiang, M., Fontaine, M. C., Perez-Casal, J., Babiuk, L. A., & Potter, A. A. (2003). Characterization of a bovine lactoferrin binding protein of Streptococcus uberis. Microbial Pathogenesis, 35, 203–215.

    Article  CAS  Google Scholar 

  • Na, Y. J., Han, S. B., Kang, J. S., Yoon, Y. D., Park, S. K., Kim, H. M., Yang, K. H., & Joe, C. O. (2004). Lactoferrin works as a new LPS-binding protein in inflammatory activation of macrophages. International Immunopharmacology, 4, 1187–1199.

    Article  CAS  Google Scholar 

  • Naidu, A. S., Andersson, M., & Forsgren, A. (1992). Identification of a human lactoferrin-binding protein in Staphylococcus aureus. Journal of Medical Microbiology, 36, 177–183.

    Article  CAS  Google Scholar 

  • Naidu, A. S., Chen, J., Martinez, C., Tulpinski, J., Pal, B. K., & Fowler, R. S. (2004). Activated lactoferrin's ability to inhibit Candida growth and block yeast adhesion to the vaginal epithelial monolayer. Journal of Reproductive Medicine, 49, 859–866.

    CAS  Google Scholar 

  • Nibbering, P. H., Ravensbergen, E., Welling, M. M., van Berkel, L. A., van Berkel, P. H., Pauwels, E. K., & Nuijens, J. H. (2001). Human lactoferrin and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant bacteria. Infection and Immunity, 69, 1469–1476.

    Article  CAS  Google Scholar 

  • Norrby, K. (2004). Human apo-lactoferrin enhances angiogenesis mediated by vascular endothelial growth factor A in vivo. Journal of Vascular Research, 41, 293–304.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Ochoa, T. J., Noguera-Obenza, M., Ebel, F., Guzman, C. A., Gomez, H. F., & Cleary, T. G. (2003). Lactoferrin impairs type III secretory system function in enteropathogenic Escherichia coli. Infection and Immunity, 71, 5149–5155.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Oh, S. M., Pyo, C. W., Kim, Y., & Choi, S. Y. (2004). Neutrophil lactoferrin upregulates the human p53 gene through induction of NF-κB activation cascade. Oncogene, 23, 8282–8291.

    Article  CAS  Google Scholar 

  • Omata, Y., Satake, M., Maeda, R., Saito, A., Shimazaki, K., Yamauchi, K., Uzuka, Y., Tanabe, S., Sarashina, T., & Mikami, T. (2001). Reduction of the infectivity of Toxoplasma gondii and Eimeria stiedai sporozoites by treatment with bovine lactoferricin. Journal of Veterinary Medical Science, 63, 187–190.

    Article  CAS  Google Scholar 

  • Penco, S., Scarfi, S., Giovine, M., Damonte, G., Millo, E., Villaggio, B., Passalacqua, M., Pozzolini, M., Garre, C., & Benatti, U. (2001). Identification of an import signal for, and the nuclear localization of, human lactoferrin. Biotechnology and Applied Biochemistry, 34, 151–159.

    Article  CAS  Google Scholar 

  • Pietrantoni, A., Di Biase, A. M., Tinari, A., Marchetti, M., Valenti, P., Seganti, L., & Superti, F. (2003). Bovine lactoferrin inhibits adenovirus infection by interacting with viral structural polypeptides. Antimicrobial Agents and Chemotherapy, 47, 2688–2691.

    Article  CAS  Google Scholar 

  • Prinz, T., Meyer, M., Pettersson, A., & Tommassen, J. (1999). Structural characterization of the lactoferrin receptor from Neisseria meningitidis. Journal of Bacteriology, 181, 4417–4419.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Qiu, J., Hendrixson, D. R., Baker, E. N., Murphy, T. F., St Geme, J. W., III, & Plaut, A. G. (1998). Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae. Proceedings of the National Academy of Sciences USA, 95, 12641–12646.

    Article  CAS  Google Scholar 

  • Reghunathan, R., Jayapal, M., Hsu, L. Y., Chng, H. H., Tai, D., Leung, B. P., & Melendez, A. J. (2005). Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome. BMC Immunology, 6, 2.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Rogan, M. P., Taggart, C. C., Greene, C. M., Murphy, P. G., O'Neill, S. J., & McElvaney, N. G. (2004). Loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity in patients with cystic fibrosis. Journal of Infectious Diseases, 190, 1245–1253.

    Article  CAS  Google Scholar 

  • Rossi, P., Giansanti, F., Boffi, A., Ajello, M., Valenti, P., Chiancone, E., & Antonini, G. (2002). Ca2+ binding to bovine lactoferrin enhances protein stability and influences the release of bacterial lipopolysaccharide. Biochemistry and Cell Biology, 80, 41–48.

    Article  CAS  Google Scholar 

  • Sakai, T., Banno, Y., Kato, Y., Nozawa, Y., & Kawaguchi, M. (2005). Pepsin-digested bovine lactoferrin induces apoptotic cell death with JNK/SAPK activation in oral cancer cells. Journal of Pharmacological Sciences, 98, 41–48.

    Article  CAS  Google Scholar 

  • Sallmann, F. R., Baveye-Descamps, S., Pattus, F., Salmon, V., Branza, N., Spik, G., & Legrand, D. (1999). Porins OmpC and PhoE of Escherichia coli as specific cell-surface targets of human lactoferrin. Binding characteristics and biological effects. Journal of Biological Chemistry, 274, 16107–16114.

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Sekine, K., Ushida, Y., Kuhara, T., Iigo, M., Baba-Toriyama, H., Moore, M. A., Murakoshi, M., Satomi, Y., Nishino, H., Kakizoe, T., & Tsuda, H. (1997). Inhibition of initiation and early stage development of aberrant crypt foci and enhanced natural killer activity in male rats administered bovine lactoferrin concomitantly with azoxymethane. Cancer Letters, 121, 211–216.

    Article  CAS  Google Scholar 

  • Sfeir, R. M., Dubarry, M., Boyaka, P. N., Rautureau, M., & Tomé, D. (2004). The mode of oral bovine lactoferrin administration influences mucosal and systemic immune responses in mice. Journal of Nutrition, 134, 403–409.

    CAS  Google Scholar 

  • Shakibaei, M., & Frevert, U. (1996). Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (LRP) and heparan sulfate proteoglycans. Journal of Experimental Medicine, 184, 1699–1711.

    Article  CAS  Google Scholar 

  • Sherman, M. P., Bennett, S. H., Hwang, F. F., & Yu, C. (2004). Neonatal small bowel epithelia: Enhancing anti-bacterial defense with lactoferrin and Lactobacillus GG. Biometals, 17, 285–289.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Shimizu, K., Matsuzawa, H., Okada, K., Tazume, S., Dosako, S., Kawasaki, Y., Hashimoto, K., & Koga, Y. (1996). Lactoferrin-mediated protection of the host from murine cytomegalovirus infection by a T-cell-dependent augmentation of natural killer cell activity. Archives of Virology, 141, 1875–1889.

    Article  CAS  Google Scholar 

  • Siciliano, R., Rega, B., Marchetti, M., Seganti, L., Antonini, G., & Valenti, P. (1999). Bovine lactoferrin peptidic fragments involved in inhibition of herpes simplex virus type 1 infection. Biochemical and Biophysical Research Communications, 264, 19–23.

    Article  CAS  Google Scholar 

  • Siebert, P. D., & Huang, B. C. (1997). Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines. Proceedings of the National Academy of Sciences USA, 94, 2198–2203.

    Article  CAS  Google Scholar 

  • Singh, P. K. (2004). Iron sequestration by human lactoferrin stimulates P. aeruginosa surface motility and blocks biofilm formation. Biometals, 17, 267–270.

    Article  CAS  Google Scholar 

  • Son, H. J., Lee, S. H., & Choi, S. Y. (2006). Human lactoferrin controls the level of retinoblastoma protein and its activity. Biochemistry and Cell Biology, 84, 345–350.

    Article  CAS  Google Scholar 

  • Son, K. N., Park, J., Chung, C. K., Chung, D. K., Yu, D. Y., Lee, K. K., & Kim, J. (2002). Human lactoferrin activates transcription of IL-1β gene in mammalian cells. Biochemical and Biophysical Research Communications, 290, 236–241.

    Article  CAS  Google Scholar 

  • Sorimachi, K., Akimoto, K., Hattori, Y., Ieiri, T., & Niwa, A. (1997). Activation of macrophages by lactoferrin: Secretion of TNF-α, IL-8 and NO. Biochemistry and Molecular Biology International, 43, 79–87.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Srivastava, M., & Pollard, H. B. (1999). Molecular dissection of nucleolin's role in growth and cell proliferation: New insights. FASEB Journal, 13, 1911–1922.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Suzuki, Y. A., Lopez, V., & Lönnerdal, B. (2005). Mammalian lactoferrin receptors: Structure and function. Cellular and Molecular Life Sciences, 62, 2560–2575.

    Article  CAS  Google Scholar 

  • Swart, P. J., Kuipers, M. E., Smit, C., Pauwels, R., deBethune, M. P., de Clercq, E., Meijer, D. K., & 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 Research and Human Retroviruses, 12, 769–775.

    CAS  Google Scholar 

  • Takayama, Y., Takahashi, H., Mizumachi, K., & Takezawa, T. (2003). Low density lipoprotein receptor-related protein (LRP) is required for lactoferrin-enhanced collagen gel contractile activity of human fibroblasts. Journal of Biological Chemistry, 278, 22112–22118.

    Article  CAS  Google Scholar 

  • Tani, F., Iio, K., Chiba, H., & Yoshikawa, M. (1990). Isolation and characterization of opioid antagonist peptides derived from human lactoferrin. Agricultural and Biological Chemistry, 54, 1803–1810.

    CAS  Google Scholar 

  • Taylor, S., Brock, J., Kruger, C., Berner, T., & Murphy, M. (2004). Safety determination for the use of bovine milk-derived lactoferrin as a component of an antimicrobial beef carcass spray. Regulatory Toxicology and Pharmacology, 39, 12–24.

    Article  CAS  Google Scholar 

  • Teng, C., Gladwell, W., Raphiou, I., & Liu, E. (2004). Methylation and expression of the lactoferrin gene in human tissues and cancer cells. Biometals, 17, 317–323.

    Article  CAS  Google Scholar 

  • Teng, C. T. (2006). Factors regulating lactoferrin gene expression. Biochemistry and Cell Biology, 84, 263–267.

    Article  CAS  Google Scholar 

  • Teng, C. T., & Gladwell, W. (2006). Single nucleotide polymorphisms (SNPs) in human lactoferrin gene. Biochemistry and Cell Biology, 84, 381–384.

    Article  CAS  Google Scholar 

  • Teng, C. T., Beard, C., & Gladwell, W. (2002). Differential expression and estrogen response of lactoferrin gene in the female reproductive tract of mouse, rat, and hamster. Biology of Reproduction, 67, 1439–1449.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Tsuda, H., Ohshima, Y., Nomoto, H., Fujita, K., Matsuda, E., Iigo, M., Takasuka, N., & Moore, M. A. (2004). Cancer prevention by natural compounds. Drug Metabolism and Pharmacokinetics, 19, 245–263.

    Article  CAS  Google Scholar 

  • Valenti, P., & Antonini, G. (2005). Lactoferrin: An important host defence against microbial and viral attack. Cellular and Molecular Life Sciences, 62, 2576–2587.

    Article  CAS  Google Scholar 

  • van Berkel, P. H., Geerts, M. E., van Veen, H. A., Mericskay, M., de Boer, H. A., & Nuijens, J. H. (1997). N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is essential for binding to heparin, bacterial lipopolysaccharide, human lysozyme and DNA. Biochemical Journal, 328 (Pt 1), 145–151.

    Google Scholar 

  • van der Kraan, M. I., van Marle, J., Nazmi, K., Groenink, J., van't Hof, W., Veerman, E. C., Bolscher, J. G., & Nieuw Amerongen, A. V. (2005). Ultrastructural effects of antimicrobial peptides from bovine lactoferrin on the membranes of Candida albicans and Escherichia coli. Peptides, 26, 1537–1542.

    Article  CAS  Google Scholar 

  • van Veen, H. A., Geerts, M. E., van Berkel, P. H., & Nuijens, J. H. (2004). The role of N-linked glycosylation in the protection of human and bovine lactoferrin against tryptic proteolysis. European Journal of Biochemistry, 271, 678–684.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Velliyagounder, K., Kaplan, J. B., Furgang, D., Legarda, D., Diamond, G., Parkin, R. E., & Fine, D. H. (2003). One of two human lactoferrin variants exhibits increased antibacterial and transcriptional activation activities and is associated with localized juvenile periodontitis. Infection and Immunity, 71, 6141–6147.

    Article  CAS  Google Scholar 

  • Viejo-Diaz, M., Andres, M. T., Perez-Gil, J., Sanchez, M., & Fierro, J. F. (2003). Potassium efflux induced by a new lactoferrin-derived peptide mimicking the effect of native human lactoferrin on the bacterial cytoplasmic membrane. Biochemistry, 68, 217–227.

    CAS  Google Scholar 

  • Visca, P., Berlutti, F., Vittorioso, P., Dalmastri, C., Thaller, M. C., & Valenti, P. (1989). Growth and adsorption of Streptococcus mutans 6715-13 to hydroxyapatite in the presence of lactoferrin. Medical Microbiology and Immunology, 178, 69–79.

    Article  CAS  Google Scholar 

  • Wakabayashi, H., Takakura, N., Teraguchi, S., & Tamura, Y. (2003). Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Microbiology and Immunology, 47, 37–43.

    CAS  Google Scholar 

  • Wakabayashi, H., Kurokawa, M., Shin, K., Teraguchi, S., Tamura, Y., & Shiraki, K. (2004). Oral lactoferrin prevents body weight loss and increases cytokine responses during herpes simplex virus type 1 infection of mice. Bioscience, Biotechnology, and Biochemistry, 68, 537–544.

    Article  CAS  Google Scholar 

  • Ward, P. P., Paz, E., & Conneely, O. M. (2005). Multifunctional roles of lactoferrin: A critical overview. Cellular and Molecular Life Sciences, 62, 2540–2548.

    Article  CAS  Google Scholar 

  • Williams, T. J., Schneider, R. P., & Willcox, M. D. (2003). The effect of protein-coated contact lenses on the adhesion and viability of Gram negative bacteria. Current Eye Research, 27, 227–235.

    Article  CAS  Google Scholar 

  • Willnow, T. E., Goldstein, J. L., Orth, K., Brown, M. S., & Herz, J. (1992). Low density lipoprotein receptor-related protein and gp330 bind similar ligands, including plasminogen activator-inhibitor complexes and lactoferrin, an inhibitor of chylomicron remnant clearance. Journal of Biological Chemistry, 267, 26172–26180.

    CAS  Google Scholar 

  • Wong, H., & Schryvers, A. B. (2003). Bacterial lactoferrin-binding protein A binds to both domains of the human lactoferrin C-lobe. Microbiology, 149, 1729–1737.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Xu, Y. Y., Samaranayake, Y. H., Samaranayake, L. P., & Nikawa, H. (1999). In vitro susceptibility of Candida species to lactoferrin. Medical Mycology, 37, 35–41.

    CAS  Google Scholar 

  • Yamaguchi, H., Abe, S., & Takakura, N. (2004). Potential usefulness of bovine lactoferrrin for adjunctive immunotherapy for mucosal Candida infections. Biometals, 17, 245–248.

    Article  CAS  Google Scholar 

  • Yamauchi, K., Wakabayashi, H., Shin, K., & Takase, M. (2006). Bovine lactoferrin: Benefits and mechanism of action against infections. Biochemistry and Cell Biology, 84, 291–296.

    Article  CAS  Google Scholar 

  • Yang, N., Strom, M. B., Mekonnen, S. M., Svendsen, J. S., & Rekdal, O. (2004). The effects of shortening lactoferrin derived peptides against tumour cells, bacteria and normal human cells. Journal of Peptide Science, 10, 37–46.

    Article  CAS  Google Scholar 

  • Yi, M., Kaneko, S., Yu, D. Y., & Murakami, S. (1997). Hepatitis C virus envelope proteins bind lactoferrin. Journal of Virology, 71, 5997–6002.

    CAS  Google Scholar 

  • Yoo, Y. C., Watanabe, R., Koike, Y., Mitobe, M., Shimazaki, K., Watanabe, S., & Azuma, I. (1997). Apoptosis in human leukemic cells induced by lactoferricin, a bovine milk protein-derived peptide: Involvement of reactive oxygen species. Biochemical and Biophysical Research Communications, 237, 624–628.

    Article  CAS  Google Scholar 

  • Yoo, Y. C., Watanabe, S., Watanabe, R., Hata, K., Shimazaki, K., & Azuma, I. (1998). Bovine lactoferrin and Lactoferricin inhibit tumor metastasis in mice. Advances in Experimental Medicine and Biology, 443, 285–291.

    CAS  Google Scholar 

  • Zagulski, T., Lipinski, P., Zagulska, A., Broniek, S., & Jarzabek, Z. (1989). Lactoferrin can protect mice against a lethal dose of Escherichia coli in experimental infection in vivo. British Journal of Experimental Pathology, 70, 697–704.

    CAS  Google Scholar 

  • Zimecki, M., Kocieba, M., & Kruzel, M. (2002). Immunoregulatory activities of lactoferrin in the delayed type hypersensitivity in mice are mediated by a receptor with affinity to mannose. Immunobiology, 205, 120–131.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unité de Glycobiologie Structurale et Fontionnelle, UMR n°8576 du CNRS, IFR 147 Université des Sciences et des Technologies de Lille, F-59655 Villeneuve d’Ascq Cedex, France

    Dominique Legrand

Authors
  1. Dominique Legrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annick Pierce
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elisabeth Elass
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mathieu Carpentier
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christophe Mariller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joël Mazurier
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Agricultural Biotechnology Center, Gödöllo, Hungary

    Zsuzsanna Bösze

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Legrand, D., Pierce, A., Elass, E., Carpentier, M., Mariller, C., Mazurier, J. (2008). Lactoferrin Structure and Functions. In: Bösze, Z. (eds) Bioactive Components of Milk. Advances in Experimental Medicine and Biology, vol 606. Springer, New York, NY. https://doi.org/10.1007/978-0-387-74087-4_6

Download citation

Publish with us

Policies and ethics

Search

Navigation