Bioactive Components of Milk pp 271-294

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

Protective Effect of Milk Peptides: Antibacterial and Antitumor Properties

  • Iván López-Expósito
  • Isidra Recio

Abstract

There is no doubt that milk proteins provide excellent nutrition for the suckling. However, apart from that, milk proteins can also exert numerous physiological activities benefiting the suckling in a variety ofways. These activities include enhancement of immune function, defense against pathogenic bacteria, viruses, and yeasts, and development of the gut and its functions. Besides the naturally occurring, biologically active proteins present in milk, a variety of bioactive peptides are encrypted within the sequence of milk proteins that are released upon suitable hydrolysis of the precursor protein. A large range of bioactivities has been reported for milk protein components, with some showing more than one kind of biological activity (Korhonen&Pihlanto, 2006). This chapter reviews the most important antimicrobial and antitumor peptides derived from milk proteins, especially those that may have a physiological significance to the suckling neonate. Antimicrobial peptides present in milk that are not derived frommilk proteins are also considered. Special attention is given to the generation of these peptides by the action of different proteolytic enzymes and the origin of these enzymes since, if present in the digestive tract, it is likely that the peptides might play a role in the host defense system. Finally, the most relevant in vivo studies carried out with this kind of bioactive peptides are discussed.

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References

  1. Almaas, H., Holm, H., Langrud, T., Flengsrud, R., & Vegarud, G.E. (2006). In vitro studies of the digestion of caprine whey proteins by human gastric and duodenal juice and the effects on selected microorganisms. British Journal of Nutrition, 96, 562–569.Google Scholar
  2. Armogida, S. A., Yannaras, N. M., Melton, A. L., & Srivastava, M. (2004). Identification and quantification of innate immune system mediators in human breast milk. Allergy and Asthma Proceedings, 25, 297–304.Google Scholar
  3. Bals, R., Wang X., Wu, Z., Freeman, T., Bafna, V., Zasloff, M., & Wilson, J. M. (1998). Human β-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. Journal of Clinical Investigation, 102, 874–880.Google Scholar
  4. Bals, R., Weiner, D. J., Moscioni, A. D., Meegalla, R. L., & Wilson, J. M. (1999). Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infection and Immunity, 67, 6084–6089.Google Scholar
  5. 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.Google Scholar
  6. Bellamy, W., Wakabayashi, H., Takase, M., Kawase, K., Shimamura, S., & Tomita, M. (1993). Killing of Candida albicans by lactoferricin-B, a potent antimicrobial peptide derived from the N-terminal region of bovine lactoferrin. Medical Microbiology and Immunology, 182, 97–105.Google Scholar
  7. Beucher, S., Levenez, F., Yvon, M., & Corring, T. (1994). Effect of caseinomacropeptide (CMP) on choleocystokinin (CCK) release by intestinal cells in rat. Journal of Nutritional Biochemistry, 5, 578–584.Google Scholar
  8. Bhimani, R. S., Vendrov, Y., & Furmanski, P. (1999). Influence of lactoferrin feeding and injection against systemic staphylococcal infections in mice. Journal of Applied Microbiology, 86, 135–144.Google Scholar
  9. Biziulevicius, G. A., & Zukaite, V. (1999). Lysosubtilin modification, Fermosob, designed for polymeric carrier-mediated intestinal delivery of lytic enzymes: Pilot-scale preparation and evaluation of this veterinary medicinal product. International Journal of Pharmacology, 189, 43–55.Google Scholar
  10. Biziulevicius, G. A., Zukaite, V., Normatiene, T., Biziuleviciene, G., & Arestov, I. (2003). Non-specific immunity-enhancing effects of tryptic casein hydrolysate versus Fermosob for treatment/prophylaxis of newborn calf colibacillosis. FEMS Immunology and Medical Microbiology, 39, 155–161.Google Scholar
  11. Bowdish, D. M. E., Davidson, D. J., & Hancock, R. E. W. (2005). A re-evaluation of the role of host defence peptides in mammalian immunity. Current Protein and Peptide Science, 6, 35–51.Google Scholar
  12. Brody, E. P. (2000). Biological activities of bovine glycomacropeptide. British Journal of Nutrition, 84, S39–S46.Google Scholar
  13. Brogden, K. A., Ackermann, M., Zabner, J., & Welsh, M. J. (2004). Antimicrobial peptides suppress microbial infection and sepsis in animal models. In R. E. W. Hancock & D. Devine (Eds.), Mammalian Host Defense Peptides (pp. 189–229). New York: Cambridge University Press.Google Scholar
  14. Chen, H., Xu, Z., Peng, L., Fang, X., Yin, X., Xu, N., & Cen, P. (2006a). Recent advances in the research and development of human defensins. Peptides, 27, 931–940.Google Scholar
  15. Chen, H. L., Yeng, C. C., Lu, C. Y., Yu, C. H., & Chen, C. M. (2006b). Synthetic porcine lactoferricin with a 20-residue peptide exhibits antimicrobial activity against Escherichia coli, Staphylococcus aureus and Candida albicans. Journal of Agricultural and Food Chemistry, 54, 3277–3282.Google Scholar
  16. Dashper, S. G., O‘Brien-Simpson, N. M., Cross, K. J., Paolini, R. A., Hoffman, B., Catmull, D. V., Malkoski, M., & Reynolds, E. C. (2005). Divalent metal cations increase the activity of the antimicrobial peptide kappacin. Antimicrobial Agents and Chemotherapy, 49, 2322–2328.Google Scholar
  17. Di Mario, F., Aragona, G., Dal Bo, N., Cavestro, G. M., Cavallaro, L., Iori, V., Comparato, G., Leandro, G., Pilotto, A., & Franze, A. (2003). Use of bovine lactoferrin for Helicobacter eradication. Digestive and Liver Disease, 35, 706–710.Google Scholar
  18. Dommett, R., Zilbauer, M., George, J. T., & Bajaj-Elliot, M. (2005). Innate immune defence in the human gastrointestinal tract. Molecular Immunology, 42, 903–912.Google Scholar
  19. Eliassen, L. T., Berge, G., Sveinbjornsson, B., Svendsen, J. S., Vorland, L. H., & Rekdal, Ø. (2002). Evidence for a direct antitumor mechanism of action of bovine lactoferricin. Anticancer Research, 22, 2703–2710.Google Scholar
  20. Eliassen, L. T., Berge, G., Leknessund, A., Wikman, M., Lindin, I., Løkke, C., Pontham, F., Johnsen, J. I., Sveinbjørnsson, B., Kogner, P., Flægstad, T., & Rekdal, Ø. (2006). The antimicrobial peptide, Lactoferricin B, is cytotoxic to neuroblastoma cells in vitro and inhibits xenograft in vivo. International Journal of Cancer, 119, 493–500.Google Scholar
  21. El-Zahar, K., Sitohy, M., Choiset, Y., Métro, F., Haertlé, T., & Chobert, J. M. (2004). Antimicrobial activity of ovine whey protein and their peptic hydrolysates. Milchwissenschaft, 59, 653–656.Google Scholar
  22. Epand, R. M., & Vogel, H. J. (1999). Diversity of antimicrobial peptides and their mechanisms of action. Biochimica et Biophysica Acta, 1462, 11–28.Google Scholar
  23. Florén, C. H., Chinenye, S., Elfstrand, L., Hagman, C., & Ihse, I. (2006). Coloplus, a new product based on bovine colostrums, alleviates HIV-associated diarrhoea. Scandinavian Journal of Gastroenterology, 41, 682–686.Google Scholar
  24. Floris, R., Recio, I., Berkhout, B., & Visser, S. (2003). Antibacterial and antiviral effects of milk proteins and derivatives thereof. Current Pharmaceutical Design, 9, 1257–1275.Google Scholar
  25. Fox, P. F. (2003). Milk proteins: General and historical aspects. In P. F. Fox & P. L. H. McSweeney (Eds.), Advanced Dairy Chemistry 1. Proteins (pp. 1–49). New York: Kluwer Academic/Plenum Publishers.Google Scholar
  26. Furlong, S. J., Mader, J. S., & Hoskin, D. W. (2006). Lactoferricin-induced apoptosis in estrogen-nonresponsive MDA-MB-435 breast cell cancer cells is enhanced by C6 ceramide or tamoxifen. Oncology Reports, 15, 1385–1390.Google Scholar
  27. Ganz, T., & Weiss, J. (1997). Antimicrobial peptides of phagocytes and epithelia. Seminars of Hematology, 34, 343–354.Google Scholar
  28. Gifford, J. L., Hunter, H. N., & Vogel, H. J. (2005). Lactoferricin: A lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties. Cell and Molecular Life Science, 62, 2588–2598.Google Scholar
  29. Goldman, M. J., Anderson, G. M., Stolzenberg, E. D., Kari, U. P., Zasloff, M., & Wilson, J. M. (1997). Human β-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell, 88, 553–560.Google Scholar
  30. Gudmundsson, G. H., Agerberth, B., Odeberg, J., Bergman, T., Olsson, B., & Salcedo, R. (1996). The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. European Journal of Biochemistry, 238, 325–332.Google Scholar
  31. Harder, J., Bartels, J., Christophers, E., & Schroder, J. M. (1997). A peptide antibiotic from human skin. Nature, 387, 861.Google Scholar
  32. Hata, I., Higashiyama, S., & Otani, H. (1998). Identification of a phosphopeptide in bovine αs1-casein digests as a factor influencing proliferation and immunoglobulin production in lymphocyte cultures. Journal of Dairy Research, 65, 569–578.Google Scholar
  33. Haukland, H. H., Ulvatne, H., Sandvik, K., & Vorland, L. H. (2001). The antimicrobial peptides lactoferricin B and magainin-2 cross over the bacterial cytoplasmic membrane and reside in the cytoplasm. FEBS Letters, 508, 389–393.Google Scholar
  34. Hayes, M., Ross, R. P., Fitzgerald, G. F., Hill, C., & Stanton, C. (2006). Casein-derived antimicrobial peptides generated by Lactobacillus acidophilus DPC6026. A pplied and Environmental Microbiology, 72, 2260–2264.Google Scholar
  35. Hernández-Ledesma, B., López-Expósito, I., Ramos, M., & Recio, I. (2006). Bioactive peptides from milk proteins. In R. Pizzano (Ed.), Immunochemistry in Dairy Research (pp. 37-60). Kerala, India: Trivandrum.Google Scholar
  36. Hill, R. D., Lahov, E., & Givol, D. (1974). A rennin-sensitive bond in alpha and beta casein. Journal of Dairy Research, 41, 147–153.Google Scholar
  37. Hirmo, S. Kelm, S., Iwersen, M., Hotta, K., Goso, Y., Ishihara, K., Suguri, T., Morita, M., Wadström, T., & Schauer, R. (1998). Inhibition of Helicobacter pylori sialic acid-specific haemagglutination by human gastrointestinal mucins and milk glycoproteins. FEMS Immunology and Medical Microbiology, 20, 275–281.Google Scholar
  38. Hoek, K., Milne, J. M., Grieve, P. A., Dionoysius, D. A., & Smith, R. (1997). Antibacterial activity of bovine lactoferrin-derived peptides. Antimicrobial Agents and Chemotherapy, 41, 54–59.Google Scholar
  39. Ibrahim, H. R. (2003). Hen egg white lysozyme and ovotransferrin: Mystery, structural role and antimicrobial function. Proceedings of the 10th European Symposium on the Quality of Eggs and Egg Products. Saint-Brieuc, France, September, pp. 1113–1128.Google Scholar
  40. Ibrahim, H. R., Thomas, U., & Pellegrini, A. (2001). A helix-loop-helix peptide at the upper lip of the active site cleft of lysozyme confers potent antimicrobial activity with membrane permeabilization action. Journal of Biological Chemistry, 276, 43767–43774.Google Scholar
  41. 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 & Experimental Metastasis, 17, 35–40.Google Scholar
  42. Isaacs, C. E. (2005). Human milk inactivates pathogens individually, additively and synergistically. Journal of Nutrition, 135, 1286–1288.Google Scholar
  43. Isamida, T., Tanaka, T., Omata, Y., Yamauchi, K., Shimazaki, K., & Saito, A. (1998). Protective effect of lactoferricin against Toxoplasma gondii infection in mice. Journal of Veterinary Medical Science, 60, 241–244.Google Scholar
  44. Isoda, H., Kawasaki, Y., Tanimoto, M., Dosako, S., & Idota, T. (1999). Use of compounds containing or binding sialic acid to neutralize bacterial toxins. European patent application no. 385112.Google Scholar
  45. Jia, H. P., Starner, T., Ackerman, M., Kirby, P., Tack, B. F., & McCray, P. B. (2001). Abundant human β-defensin-1 expression in milk and mammary gland epithelium. Journal of Pediatrics, 138, 109–112.Google Scholar
  46. Kampa, M., Bakogeorgou, E., Hatzoglou, A., Damianaki, A., Martin, P. M., & Castanas, E. (1997). Opioid alkaloids and casomorphin peptides decrease the proliferation of prostatic cells lines (LNCaP, PC3 and DU145) through a partial interaction with opioid receptors. European Journal of Pharmacology, 335, 255–265.Google Scholar
  47. Kawaguchi, S., Hayashi, T., Masano, H., Okuyama, K., Suzuki, T., & Kawase, K. (1989). Effect of lactoferrin-enriched infant formula on low birth weight infants [in Japanese]. Shuusnakiigaku, 19, 125–130.Google Scholar
  48. Kawasaki, Y., Isoda, H., Tanimoto, M., Dosako, S., Idota, T., & Ahiko, K. (1992). Inhibition by lactoferrin and κ-casein glycomacropeptide of binding of cholera toxin to its receptor. Biotechnology and Biochemistry, 56, 195–198.Google Scholar
  49. Kawasaki, Y., Isoda, K., Shinmoto, H., Tanimoto, M., Dosako, S., Idota, T., & Nakajima, I. (1993). Inhibition by κ-casein glycomacropeptide and lactoferrin of influenza virus hemaglutination. Bioscience, Biotechnology and Biochemistry, 57, 1214–1215.Google Scholar
  50. Korhonen, H., & Pihlanto, A. (2006). Bioactive peptides: Production and functionality. International Dairy Journal, 16, 945–960.Google Scholar
  51. Kuwata, H., Yip, T. T., Tomita, M., & Hutchens, T. W. (1998a) Direct evidence of the generation in human stomach of an antimicrobial peptide domain (lactoferricin) from ingested lactoferrin. Biochimica et Biophysica Acta, 1429, 129–141.Google Scholar
  52. Kuwata, H., Yip, T. T., Yamauchi, K., Teraguchi, S., Hayasawa, H., Tomita, M., & Hutchens, T. W. (1998b). The survival of ingested lactoferrin in the gastrointestinal tract of adult mice. Biochemistry Journal, 334, 321–323.Google Scholar
  53. Lahov, E., & Regelson W. (1996). Antibacterial and immunostimulating casein-derived substances from milk: Casecidin, isracidin peptides. Federal Chemistry Toxicology, 34, 131–145.Google Scholar
  54. Ledoux, N., Mahé, S., Dubarry, M., Bourras, M., Benamouzig, R., & Tomé, D. (1999). Intraluminal immunoreactive caseinomacropeptide after milk protein ingestion in humans. Nahrung, 43, 196–200.Google Scholar
  55. Lee, H. Y., Park, J. H., Seok, S. H., Baek, M. W., Kim, D. J., Lee, B. H., Kang, P. D., Kim, Y. S., & Park, J. H. (2005). Potencial antimicrobial effects of human lactoferrin against oral infection with Listeria monocytogenes in mice. Journal of Medical Microbiology, 54, 1049–1054.Google Scholar
  56. Lehrer, R. I., & Ganz, T. (2002). Defensins of vertebrate animals. Current Opinion in Immunology, 14, 96–102.Google Scholar
  57. Lehrer, R. I., Lichtenstein, A. K., & Ganz, T. (1993). Defensins: Antimicrobial and cytotoxic peptides of mammalian cells. Annual Reviews in Immunology, 11, 105–128.Google Scholar
  58. León-Sicarios, N., Reyes-López, M., Ordaz-Pichardo, C., & de la Garza, M. (2006). Microbicidal action of lactoferrin and lactoferricin and their synergistic effect with metronizadole in Entoamoeba histolytica. Biochemistry and Cell Biology, 84, 327–336.Google Scholar
  59. Levay, P. F., & Viljoen, M. (1995). Lactoferrin, a general review. Haematologica, 80, 252–267.Google Scholar
  60. Liepke, C., Zucht, H. D., Forssman, W. G., & Ständker, L. (2001). Purification of novel peptide antibiotics from human milk. Journal of Chromatography B, 752, 369–377.Google Scholar
  61. López-Expósito, I., & Recio, I. (2006). Antibacterial activity of peptides and folding variants from milk proteins. International Dairy Journal, 16, 1294–1305.Google Scholar
  62. López-Expósito, I., Gómez-Ruiz, J. A., Amigo, L., & Recio, I. (2006a). Identification of antibacterial peptides from ovine αs2-casein. International Dairy Journal, 16, 1072–1080.Google Scholar
  63. López-Expósito, I., Minervini, F., Amigo, L., & Recio, I. (2006b). Identification of antibacterial peptides from bovine κ-casein. Journal of Food Protection, 69, 2992–2997.Google Scholar
  64. López-Expósito, I. (2007a). Novel peptides with antibacterial activity derived from food proteins. Study of the mode of action and synergistic effect. Dissertation Tesis. Faculty of Science. Universidad Autónoma de Madrid.Google Scholar
  65. López-Expósito, I., Pellegrini, A., Amigo, L., & Recio, I. (2007b). Synergistic effect between different milk-derived peptides and proteins. Journal of Dairy Science (submitted).Google Scholar
  66. López-Expósito, I., Quirós, A., Amigo, L., & Recio, I. (2007c). Casein hydrolysates as source of antimicrobial, antioxidant and antihypertensive peptides. Le Lait (in press).Google Scholar
  67. Mader, J. S., Salsman, J., Conrad, D. M., & Hoskin, D. W. (2005). Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cells lines. Molecular Cancer Therapy, 4, 612–624.Google Scholar
  68. Mader, J. S., Smyth, D., Marshall, J., & Hoskin, D. W. (2006). Bovine lactoferricin inhibits basic fibroblast growth factor- and vascular endothelial growth factor165–induced angiogenesis by competing for heparin-like binding sites on endothelial cells. American Journal of Pathology, 169, 1753–1766.Google Scholar
  69. Malkoski, M., Dashper, S. G., O‘Brien-Simpson, N. M., Talbo, G. H., Macris, M., Cross, K. J., & Reynolds, E. C. (2001). Kappacin, a novel antimicrobial peptide from bovine milk. Antimicrobial Agents and Chemotherapy, 45, 2309–2315.Google Scholar
  70. Marshall, K. (2004). Therapeutic applications of whey protein. Alternative Medicine Review, 9, 136–156.Google Scholar
  71. Masschalck, B., & Michiels, C. W. (2003). Antimicrobial properties of lysozyme in relation to foodborne vegetative bacteria. Critical Reviews in Microbiology, 29, 191–214.Google Scholar
  72. Matin, A., & Otani, H. (2002). Cytotoxic and antibacterial activities of chemically synthesized κ-casecidin and its partial peptide fragments. Journal of Dairy Research, 69, 329–334.Google Scholar
  73. McCann, K. B., Shiell, B. J., Michalski, W. P., Lee, A., Wan, J., Roginski, H., & Coventry, M. J. (2006). Isolation and characterisation of a novel antibacterial peptide from bovine αs1-casein. International Dairy Journal, 16, 316–323.Google Scholar
  74. Meisel, H. (2005). Biochemical properties of peptides encrypted in bovine milk proteins. Current Medicinal Chemistry, 12, 1905–1919.Google Scholar
  75. Minervini, F., Algaron, F., Rizzello, C. G., Fox, P. F., Monnet, V., & Gobetti, M. (2003). Angiotensin I-converting-enzyme-inhibitory and antibacterial peptides from Lactobacillus helveticus PR4 proteinase-hydrolyzed caseins of milk from six species. Applied and Environmental Microbiology, 69, 5297–5305.Google Scholar
  76. Muñoz, A., & Marcos, J. F. (2006). Activity and mode of action against fungal phytopathogens of bovine lactoferrin-derived peptides. Journal of Applied Microbiology, 101, 1199–1207.Google Scholar
  77. Murakami, M., Dorschner, R. A., Stern, L. J., Lin, K. H., & Gallo, R. L. (2005). Expression and secretion of cathelicidin antimicrobial peptides in murine mammary glands and human milk. Pediatric Research, 57, 10–15.Google Scholar
  78. Nakasone, Y., Adjei, A., Yoshise, M., Yamauchi, K., Takase, M., Yamauchi, K., Shimamura, S., & Yamamoto, S. (1994). Effect of dietary lactoferricin on the recovery of mice infected with methicillin-resistant Staphylococcus aureus. Abstract Annual Meeting of the Japanese Society of Nutritional Food Science [in Japanese], p. 50.Google Scholar
  79. Nazarowec-White, M., & Farber, J. M. (1997). Thermal resistance of Enterobacter sakazakii in reconstituted dried infant formula. Letters in Applied Microbiology, 24, 9–13.Google Scholar
  80. Newburg, D. S. (2005). Innate immunity and human milk. Journal of Nutrition, 135, 1308–1312.Google Scholar
  81. Okumura, K., Itoh, A., Isogai, E. Hirose, K., Hosokawa, Y., Abiko, Y., Shibata, T., Hirata, M., & Isogai, H. (2004). C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells. Cancer Letters, 212, 185–194.Google Scholar
  82. Otani, H., & Suzuki, H. (2003). Isolation and characterization of cytotoxic small peptides, α-casecidins, from bovine αs1-casein digested with bovine trypsin. Animal Science Journal, 74, 427–435.Google Scholar
  83. Pakkanen, R., & Aalto, J. (1997). Growth factors and antimicrobial factors of bovine colostrums. International Dairy Journal, 7, 285–297.Google Scholar
  84. Pellegrini, A. (2003). Antimicrobial peptides from food proteins. Current Pharmaceutical Design, 9, 1225–1238.Google Scholar
  85. Pellegrini, A., Thomas, U., Bramaz, N., Klauser, S., Humziker, P., & von Fellenberg, R. (1997). Identification and isolation of a bactericidal domain in chicken egg white lysozyme. Journal of Applied Microbiology, 82, 372–378.Google Scholar
  86. Pellegrini, A., Thomas, U, Bramaz, N., Hunziker, P., & Von Fellenberg, R. (1999). Isolation and identification of three bactericidal domains in the bovine α–lactalbumin molecule. Biochimica et Biophysica Acta, 1426, 439–448.Google Scholar
  87. Pellegrini, A., Dettling, C., Thomas, U., & Hunziker, P. (2001). Isolation and characterization of four bactericidal domains in the bovine β-lactoglobulin. Biochimica et Biophysica Acta, 1526, 131–140.Google Scholar
  88. Piertrantoni, A., Ammendolia, M. G., Tinari, A., Siciliano, R., Valenti, P., & Superti, F. (2006). Bovine lactoferrin peptidic fragments envolved in inhibition of Echovirus 6 in vitro infection. Antiviral Research, 69, 98–106.Google Scholar
  89. Porter, E. M., Dam, E. V., Valore, E. V., & Ganz, T. (1997). Broad-spectrum antimicrobial activity of human intestinal defensin 5. Infection and Immunology, 65, 2396–2401.Google Scholar
  90. Prouxl, M., Gauthier, S. F., & Roy, D. (1992). Effect of casein hydrolysates on the growth of bifidobacteria. Le Lait, 72, 393–404.Google Scholar
  91. Recio, I., & Visser, S. (1999a). Identification of two distinct antibacterial domains within the sequence of bovine αs2-casein. Biochimica et Biophysica Acta, 1428, 314–326.Google Scholar
  92. Recio, I., & Visser, S. (1999b). Two ion-exchange chromatographic methods for the isolation of antibacterial peptides from lactoferrin. In situ enzymatic hydrolysis on an ion-exchange membrane. Journal of Chromatography A, 831, 191–201.Google Scholar
  93. Recio, I., & Visser, S. (2000). Antibacterial and binding characteristics of bovine, ovine and caprine lactoferrins: A comparative study. International Dairy Journal, 10, 597–605.Google Scholar
  94. Recio, I., Quirós, A., Hernández-Ledesma, B., Gómez-Ruiz, J. A., Miguel, M., Amigo, L., López-Expósito, I., Ramos, M., & Aleixandre, A. (2005). Bioactive peptides identified in enzyme hydrolysates from milk caseins and procedure for their obtention. Spanish patent application ES200501373.Google Scholar
  95. Roy, M. K., Watanabe, Y., & Tamai, Y. (1999). Induction of apoptosis in HL-60 cells by skimmed milk digested with a proteolytic enzyme from the yeast Saccharomyces cerevisiae. Journal of Bioscience Bioengineering, 88, 426–432.Google Scholar
  96. Roy, M. K., Kuwabara, Y., Hara, K., Watanabe, Y., & Tamai, Y. (2002). Peptides from the N-terminal end of bovine lactoferrin induce apoptosis in human leukemic (HL-60) cells. Journal of Dairy Science, 85, 2065–2074.Google Scholar
  97. Salzman, N. H., Polin, R. A., Harris, M. C., Ruchelli, E., Hebra, A., Zirin-Butler, S., Jawad, A., Porter, E. M., & Bevins, C. L. (1998). Enteric defensin expression in necrotizing enterocolitis. Pediatric Research, 44, 20–26.Google Scholar
  98. Schiffer, M., Chang, C. H., & Stevens, F. J. (1992). The functions of tryptophan residues in membrane proteins. Protein Engineering, 5, 213–214.Google Scholar
  99. Schupbach, P., Neeser, J. R., Golliard, M., Rouvet, M., & Guggenheim, B. (1996). Incorporation of caseinoglycomacropeptide and caseinophosphopeptide into the salivary pellicle inhibits adherence of mutans streptococci. Journal of Dental Research, 75, 1779–1788.Google Scholar
  100. Smith, J. A., Wilkinson, M. C., & Liu, Q. M. (1997). Casein fragments having growth promoting activity. International patent WO 97/16460. Google Scholar
  101. Strøm, M. H., Haug, B. E., Rekdal, O., Skar, M. L., Stensen, W., & Svendsen, J. S. (2002). Important structural features of 15 residue lactoferricin derivatives and methods for improvement of antimicrobial activity. Biochemistry and Cell Biology, 80, 65–74.Google Scholar
  102. Teraguchi, S., Ozawa, K., Yasuda, S., Shin, K., Fukuwatari, Y., & Shimamura, S. (1994). The bacteriostatic effects of orally administered bovine lactoferrin on intestinal Enterobacteriaceae of SPF mice fed bovine milk. Bioscience, Biotechnology and Biochemistry, 58,482–487.Google Scholar
  103. Teraguchi, S., Shin, K., Ogata, T., Kingaku, M., Kaino, A., Miyauchi, H., Fukuwatari, Y., & Shimamura, S. (1995). Orally administered bovine lactoferrin inhibits bacterial translocation in mice fed bovine milk. Applied and Environmental Microbiology, 61, 4131–4134.Google Scholar
  104. Tomita, M., Wakabayashi, H., Yamauchi, K., Teraguchi, S., & Hayasawa, H. (2002). Bovine lactoferrin and lactoferricin derived from milk: Production and applications. Biochemistry and Cell Biology, 80, 109–112.Google Scholar
  105. Tunzi, C. R., Harper, P. A., Bar-Oz, B., Valore, E. V., Semple, J. L., Watson-MacDonell, J., Ganz, T., & Ito, S. (2000). β-Defensin expression in human mammary gland epithelia. Pediatric Research, 48, 30–35.Google Scholar
  106. Turner, J., Cho, Y. Dinh, N. N., Waring, A. J., & Lehrer, R. I. (1998). Activities of LL37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrobial Agents and Chemotherapy, 42, 2206–2214.Google Scholar
  107. Ulvatne, H., Samuelsen, Ø., Haukland, H. H., Krämer, M., & Vorland, L. H. (2004). Lactoferricin B inhibits bacterial macromolecular synthesis in Escherichia coli and Bacillus subtilis. FEMS Microbiology Letters, 237, 377–384.Google Scholar
  108. Valore, E. V., Park, C. H., Quayle, A. J., Wiles, K. R., McCray, P. B., & Ganz, T. (1998). Human β-defensin-1, an antimicrobial peptide of urogenital tissues. Journal of Clinical Investigation, 101, 1633–1642.Google Scholar
  109. van der Kraan, M. I. A., Groenink, J., Nazmi, K., Veerman, E. C. I., Bolscher, J. G. M., & Nieuw Amerongen, A. V. (2004). Lactoferrampin: A novel antimicrobial peptide in the N1-domain of bovine lactoferrin. Peptides, 25, 177–183.Google Scholar
  110. van Hooijdonk, A. C. M., Kussendrager, K. D., & Steijns, J. M. (2000). In vivo antimicrobial and antiviral activity of components in bovine milk and colostrums involved in non-specific defence. British Journal of Nutrition, 84, 127–134.Google Scholar
  111. Vogel, H. J., Schibli, D. J., Weiguo, J., Lohmeier-Vogel, E. M., Epand, R. F., & Epand, R. M. (2002). Towards a structure-function analysis of bovine lactoferricin and related tryptophan and arginine containing peptides. Biochemistry and Cell Biology, 80, 49–63.Google Scholar
  112. Vorland, L. H., Ulvatne, H., Andersen, J., Haukland, H. H., Rekdal, Ø., Svendsen, J. S., & Gutteberg, T. J. (1998). Lactoferricin of bovine origin is more active than lactoferricins of human, murine and caprine origin. Scandinavian Journal of Infectious Diseases, 30, 513–517.Google Scholar
  113. Vorland, L. H., Ulvatne, H., Rekdal, Ø., & Svendsen, J. S. (1999). Initial binding sites of antimicrobial peptides in Staphylococcus aureus and Escherichia coli. Scandinavian Journal of Infectious Diseases, 31, 467–473.Google Scholar
  114. Wakabayashi, H., Takase, M., & Tomita, M. (2003). Lactoferricin derived from milk protein lactoferrin. Current Pharmaceutical Design, 9, 1277–1287.Google Scholar
  115. Wakabayashi, H., Kuwata, H., Yamauchi, K., Teraguchi, S., & Yoshitaka, T. (2004). No detectable transfer of dietary lactoferrin or its multifunctional fragments to portal blood in healthy adults rats. Bioscience, Biotechnology and Biochemistry, 68, 853–860.Google Scholar
  116. Wakabayashi, H., Yamauchi, K., & Takase, M. (2006). Lactoferrin: Research, technology and applications. International Dairy Journal, 16, 1241–1251.Google Scholar
  117. Yamauchi, K., Tomita, M., Giehl, T. J., & Ellison, R. T., III (1993). Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. Infection and Immunity, 61, 719–728.Google Scholar
  118. Yang, D., Chertov, O., Bykovskaia, S. N., Chen, Q., Buffo, M. J., Shogan, J., Anderson, M., Schroder, J. M., Wang, J. M., Howard, O. M. Z., & Oppenheim, J. J. (1999). Beta-defensins: Linking innate and adaptative immunity through dendritic and T-cell CCR6. Science, 286, 525–528.Google Scholar
  119. Yang, N., Strøm, M. B., Mekonnen, S. M., Svendsen, J. S., & Rekdal, Ø. (2004). The effects of shortening lactoferrin derived peptides against tumour cells, bacteria and normal human cells. Journal of Peptide Science, 10, 37–46.Google Scholar
  120. Zaiou, M., Nizet, V., & Gallo, R. L. (2003). Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL37) prosequence. Journal of Investigation in Dermatology, 120, 810–816.Google Scholar
  121. Zanetti, M. (2004). Cathelicidins, multifunctional peptides of the innate immunity. Journal of Leukocyte Biology, 75, 39–48.Google Scholar
  122. Zasloff, M. (2002). Antimicrobial peptides of multicellular organisms. Nature, 415, 389–395.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Iván López-Expósito
  • Isidra Recio
    • 1
  1. 1.Instituto de Fermentaciones Industriales (CSIC)28006 MadridSpain

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