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The role of lactoferrin in the gastrointestinal tract

  • Chapter
Recent Developments in Infant Nutrition

Part of the book series: Tenth Nutricia Symposium ((NUSY,volume 9))

Abstract

Lactoferrin is an iron-binding glycoprotein that consists of a single polypeptide chain with a molecular weight of 78 kDa. It is the second most abundant protein in human milk (~ 1g/l) (1,2) and is found in most exocrine secretions including tears, nasal secretions, saliva, intestinal mucus and genital secretions (3–5). The protein also is expressed and secreted by the secondary granules of polymorphonuclear neutrophils (6). The polypeptide structure of lactoferrin comprises two homologous domains that appear to have arisen by intragenic duplication (7). The crystal structure of the protein has been resolved (8,9) and it has been shown that each domain binds one ferric and one carbonate anion. In addition, each domain contains one glycosylated site to which N-linked glycan residues are attached (10).

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Abbreviations

LPS:

lipopolysaccharides

nLF:

native human lactoferrin

rLF:

recombinant human lactoferrin

References

  1. Masson PL, Heremans JF 1971 Lactoferrin in milk from different species. Comp Biochem Physiol 39:119–129

    CAS  Google Scholar 

  2. Hennart PF, Brasseur DJ, Delogne-Desnoeck JB, Dramaix MM, Robyn CE 1991 Lysozyme, lactoferrin and secretory immunoglobin A content in breast milk: Influence of duration of lactation, nutrition status, prolactin status, and parity of mother. Am J Clin Nutr 53:32–39

    PubMed  CAS  Google Scholar 

  3. Masson PL, Heremans JF, Dive C 1966 An iron-binding protein common to many external secretions. Clin Chim Acta 14:735–739

    Article  CAS  Google Scholar 

  4. Pentecost BT, Teng CT 1987 Lactotransferrin is the major estrogen inducible protein of mouse uterine secretions. J Biol Chem 262:10134–10139

    PubMed  CAS  Google Scholar 

  5. Yu L-C, Chen Y-H 1993 The developmental profile of lactoferrin in mouse epididymis. Biochem J 296:107–111

    PubMed  CAS  Google Scholar 

  6. Masson PL, Heremans JF, Schonne E 1969 Lactoferrin, an iron-binding protein in neutrophilic leukocytes. J Exp Med 130:643–658

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Anderson BF, Baker HM, Norris GE, Rice DW, Baker EN 1989 Structure of human lactoferrin: Crystallographic structure analysis and refinement at 2.8Å resolution. J Mol Biol 209:711–734

    Article  PubMed  CAS  Google Scholar 

  9. Anderson BF, Baker HM, Norris GE, Rumball SV, Baker EN 1990 Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins. Nature 344:784–787

    Article  PubMed  CAS  Google Scholar 

  10. Spik G, Coddenville B, Montreuil J 1988 Comparative study of the primary structures of sero-, lacto- and ovotransferrin glycans from different species. Biochemistry 70:1459–1469

    Article  CAS  Google Scholar 

  11. Aisen P, Listowsky I 1980 Iron transport and storage proteins. Annu Rev Biochem 49:357–393

    Article  PubMed  CAS  Google Scholar 

  12. MacGillivray RTA, Mendez E, Shewale JG, Sinha SK, Lineback-Zins J, Brew J 1983 The primary structure of serum transferrin. J Biol Chem 258:3543–3553

    PubMed  CAS  Google Scholar 

  13. Yang F, Lum JB, McGill JR, Moore CM, Naylor SL, Van Bragt PH, Baldwin WD, Bowman BH 1984 Human transferrin: cDNA characterization and chromosomal location. Proc Natl Acad Sci USA 81:2752–2756

    Article  PubMed  CAS  Google Scholar 

  14. Jeltsch J-M, Chambon P 1982 The complete nucleotide sequence of the chick ovotransferrin mRNA. Eur J Biochem 122:291–295

    Article  PubMed  CAS  Google Scholar 

  15. Rose TM, Plowman GD, Teplow DB, Dreyer WJ, Hellström K-E, Brown JP 1986 Primary structure of the human melanoma-associated antigen p97 (melanotransferrin) deduced from mRNA sequence. Proc Natl Acad Sci USA 83:1261–1265

    Article  PubMed  CAS  Google Scholar 

  16. Aisen P, Leibman A 1972 Lactoferrin and transferrin: A comparative study. Biochim Biophys Acta 257:314–323

    PubMed  CAS  Google Scholar 

  17. Mazurier J, Spik G 1989 Comparative study of the iron-binding properties of human transferrins. I. Complete and sequential iron saturation and desaturation of the lactotransferrin. Biochim Biophys Acta 629:399–408

    Article  Google Scholar 

  18. Sanchez L, Calvo M, Brock JH 1992 Biological role of lactoferrin. Arch Dis Child 67:657–661

    Article  PubMed  CAS  Google Scholar 

  19. Iyer S, Lönnerdal B 1993 Lactoferrin, lactoferrin receptors and iron metabolism. Eur J Clin Nutr 47:232–241

    PubMed  CAS  Google Scholar 

  20. Fransson G-B, Lönnerdal B 1980 Iron in human milk. J Pediatr 96:380–384

    Article  PubMed  CAS  Google Scholar 

  21. Davidson LA, Lönnerdal B 1989 Fe-saturation and proteolysis of human lactoferrin: effect on brush-border receptor-mediated uptake of Fe and Mn. Am J Physiol 257:G930-G934

    PubMed  CAS  Google Scholar 

  22. Nichols BL, McKee KS, Huebers HA 1990 Iron is not required in the lactoferrin stimulation of thymidine incorporation into the DNA of rat crypt enterocytes. Pediatr Res 27:525–528

    Article  PubMed  CAS  Google Scholar 

  23. Nemet K, Simonovits I 1985 The biological role of lactoferrin. Haematologia 18:3–12

    PubMed  CAS  Google Scholar 

  24. Weinberg ED 1978 Iron and infection. Microbiol Rev 42:45–66

    PubMed  CAS  Google Scholar 

  25. Bullen JJ, Rogers HJ, Leigh L 1971 Iron-binding proteins in milk and resistance to Escherichia coli infections in infants. Br Med J 1:69–75

    Article  Google Scholar 

  26. Zucali JR, Broxmeyer HE, Levy D, Morse C 1989 Lactoferrin decreases monocyte-induced fibroblast production of myeloid colony-stimulating activity by suppressing monocyte release of interleukin-1. Blood 74:1531–1536

    PubMed  CAS  Google Scholar 

  27. Hangoc G, Falkenburg JHF, Broxmeyer HE 1991 Influence of T-lymphocytes and lactoferrin on the survival promoting effects of IL-1 and IL-6 on human bone marrow granulocyte-macrophage and erythroid progenitor cells. Exp Hematol 19:697–703

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  29. Crouch SPM, Slater KJ, Fletcher J 1992 Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood 80:235–240

    PubMed  CAS  Google Scholar 

  30. Cox TM, Mazurier J, Spik G, Montreuil J, Peters TJ 1979 Iron binding proteins and influx of iron across the duodenal brush border. Evidence for specific lactotransferrin receptors in the human intestine. Biochem Biophys Acta 558:120–128

    Google Scholar 

  31. Hu WL, Mazurier J, Sawatzki G, Montreuil J, Spik G 1988 Lactotransferrin receptor of mouse small-intestinal brush border: binding characteristics of membrane-bound and Triton X-100-solubilized forms. Biochem J 249:435–441

    PubMed  CAS  Google Scholar 

  32. Hu WL, Mazurier J, Spik G 1990 Isolation and partial characterization of a lactotransferrin receptor from mouse intestinal brush border. Biochemistry 29:535–541

    Article  PubMed  CAS  Google Scholar 

  33. Spik G, Strecker G, Fournet B, Bouquelet S, Montreuil J, Dorland L, van Halbeek H, Vliegenthart JFG 1982 Primary structure of the glycans from human lactotransferrin. Eur J Biochem 121: 413–419

    Article  PubMed  CAS  Google Scholar 

  34. Arnold RR, Cole MF, McGhee JR 1977 A bactericidal effect for human lactoferrin. Science 197: 263–265

    Article  PubMed  CAS  Google Scholar 

  35. Oram JD, Reiter B 1968 Inhibition of bacteria by lactoferrin and other iron-chelating agents. Biochim Biophys Acta 170:351–365

    Article  PubMed  CAS  Google Scholar 

  36. Arnold RR, Brewer M, Gauthier JJ 1980 Bactericidal activity of human lactoferrin: Sensitivity of a variety of microorganisms. Infect Immun 28:893–898

    PubMed  CAS  Google Scholar 

  37. Trümpier U, Straub PW, Rosenmund A 1989 Antibacterial prophylaxis with lactoferrin in neutropenic patients. Eur J Clin Microbiol Infect Dis 8:310–313

    Article  Google Scholar 

  38. 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. Br J Exp Pathol 70:697–704

    PubMed  CAS  Google Scholar 

  39. Bullen JJ, Rogers HJ, Griffiths E 1978 Role of iron in bacterial infection. Curr Topics Microbiol Immunol 80:1–35

    Article  CAS  Google Scholar 

  40. Reiter B 1978 Review of non-specific antimicrobial factors in milk. Ann Rech Vet 9:205–224

    PubMed  CAS  Google Scholar 

  41. Reiter B, Brock JH, Steel ED 1975 Inhibition of E. coli by bovine colostrum and post-colostral milk. II. The bacteristatic effect of LF on a serum susceptible and serum resistant strain of E. coli. Immunology 28:83–95

    PubMed  CAS  Google Scholar 

  42. Griffiths E, Humphreys J 1977 Bacteriostatic effect of human milk and bovine colostrum on Escherichia coli: Importance of bicarbonate. Infect Immun 15:396–401

    PubMed  CAS  Google Scholar 

  43. Arnold RR, Russell JE, Champion WJ, Gauthier JJ 1981 Bactericidal activity of human lactoferrin: Influence of physical conditions and metabolic conditions of the target microorganism. Infect Immun 32:655–660

    PubMed  CAS  Google Scholar 

  44. Ellison RT, Giehl T-J, La Force FM 1988 Damage of the outer membrane of enteric Gram-negative bacteria by lactoferrin and transferrin. Infect Immun 56:2774–2781

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  46. Yamauchi K, Tomita M, Giehl TJ, Ellison RT 1993 Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. Infect Immun 61:719–728

    PubMed  CAS  Google Scholar 

  47. Zasloff M 1987 Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms and partial cDNA sequence of a precursor. Proc Natl Acad Sci USA 84:5449–5453

    Article  PubMed  CAS  Google Scholar 

  48. Sawatzki G, Rich C 1989 Lactoferrin stimulates colony stimulating factor production in vitro and in vivo. Blood Cells 15:371–375

    PubMed  CAS  Google Scholar 

  49. Broxmeyer HE, Williams DE, Hangoc G, Cooper S, Gentile P, Shen RN, Ralph P, Gillis S, Bicknell DC 1987 The opposing actions in vivo on murine myelopoiesis of purified preparations of lactoferrin and the colony stimulating factors. Blood Cells 13:31–48

    PubMed  CAS  Google Scholar 

  50. Zucali JR, Broxmeyer HE, Ulatowski JA 1979 Specificity of lactoferrin as an inhibitor of granulocyte-macrophage colony-stimulating activity production from fetal mouse liver cells. Blood 54:951–954

    PubMed  CAS  Google Scholar 

  51. Breton-Gorius J, Mason DY, Buriot D, Vilde JL, Griscelli C 1980 Lactoferrin deficiency as a consequence of a lack of specific granules in neutrophils from a patient with recurrent infections. Am J Pathol 99:413–419

    PubMed  CAS  Google Scholar 

  52. Boxer LA, Coates TD, Haak RA, Wolach JB, Hoffstein S, Baehner RL 1982 Lactoferrin deficiency associated with altered granulocyte function. New Engl J Med 307:404–409

    Article  PubMed  CAS  Google Scholar 

  53. Gutteberg TJ, Rokke O, Andersen O, Jørgensen T 1989 Early fall of circulating iron and rapid rise of lactoferrin in septicemia and endotoxemia: An early defence mechanism. Scand J Infect Dis 21:709–715

    Article  PubMed  CAS  Google Scholar 

  54. Wang D, Pabst KM, Aida Y, Pabst MJ 1995 Lipopolysaccharide-inactivating activity of neutrophils is due to lactoferrin. J Leukoc Biol 57:865–874

    PubMed  CAS  Google Scholar 

  55. Birgens HS, Hansen NE, Karle H, Kristensen LO 1983 Receptor binding of lactoferrin by human monocytes. Br J Haematol 54:383–391

    Article  PubMed  CAS  Google Scholar 

  56. van Snick JL, Masson PL 1976 Binding of human lactoferrin to mouse peritoneal cells. J Exp Med 144:1568–1580

    Article  PubMed  Google Scholar 

  57. Leveugle B, Mazurier J, Legrand D, Mazurier C, Montreuil J, Spik G 1993 Lactotransferrin binding to its platelet receptor inhibits platelet aggregation. Eur J Biochem 213:1205–1211

    Article  PubMed  CAS  Google Scholar 

  58. Mazurier J, Legrand D, Hu WL, 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. Eur J Biochem 179:481–487

    Article  PubMed  CAS  Google Scholar 

  59. Ward PP, Piddington CS, Cunningham GA, Zhou X, Wyatt RO, Conneely OM 1995 A system for production of commercial quantities of human lactoferrin: a broad spectrum natural antibiotic. Biotechnology 13:498–503

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. O. M. Conneely
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  2. P. P. Ward
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  3. X. Zhou
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  4. S. Wagner
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Editor information

Editors and Affiliations

  1. Nutricia Research, PO Box 1, 2700 MA, Zoetermeer, The Netherlands

    J. G. Bindels  & A. C. Goedhart  & 

  2. Ghisebrecht Bokellaan 29, 3054 CA, Rotterdam, The Netherlands

    H. K. A. Visser

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© 1996 Kluwer Academic Publishers

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Conneely, O.M., Ward, P.P., Zhou, X., Wagner, S. (1996). The role of lactoferrin in the gastrointestinal tract. In: Bindels, J.G., Goedhart, A.C., Visser, H.K.A. (eds) Recent Developments in Infant Nutrition. Tenth Nutricia Symposium, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-1790-3_25

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  • DOI: https://doi.org/10.1007/978-94-009-1790-3_25

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-7298-4

  • Online ISBN: 978-94-009-1790-3

  • eBook Packages: Springer Book Archive

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