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Physical Characteristics and Polymerization During Iron Saturation of Lactoferrin, A Myelopoietic Regulatory Molecule with Suppressor Activity

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Lactoferrin

Part of the book series: Advances in, Experimental Medicine and Biology ((AEMB,volume 357))

Abstract

Lactoferrin (LF) has been implicated in normal regulation of myeloid blood cell production in vitro and in vivo and abnormalities in LF-cell interactions have been associated with progression of leukemia and other hematopoietic disorders. LF may be clinically useful and for this reason we studied selected biochemical characteristics of LF. Purified human milk LF was saturated with iron from solution and analyzed by gel electrophoresis, ion-exchange and gel filtration chromatography. The metalloprotein was found to contain several molecular weight species on polyacrylamide gels. High resolution ion-exchange chromatography demonstrated the binding of LF to both anionic and cationic media under identical conditions indicating a bipolar charge distribution. Gel filtration studies revealed a tetramerized form of LF, the formation and stability of which was dependent on the ionic strength of the solution.

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References

  1. Metz-Boutique MH, Jolies J, Mazurier J, Schoentgen F, Legrand D, Spik G, Montreuil J, Jolies P (1984) Human lactoferrin: amino acid sequence and structural comparisons with other transferons. Eur J Bio-chem 145:659–676.

    Article  Google Scholar 

  2. 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 

  3. Kijlstra A, Kuizenga A, van der Velde M., van Haeringen NJ (1989) Gel electrophoresis of human tears reveals various forms of tear lactoferrin. Curr Eye Res 8:581–588.

    Article  PubMed  CAS  Google Scholar 

  4. Bennett RM, Eddie-Quartey AC, Holt PJL (1973) Lactoferrin-an iron binding protein in synovial fluid. Arthritis Rheum 16:186–190.

    Article  PubMed  CAS  Google Scholar 

  5. Broxmeyer HE, Gentile P, Bognacki J, Ralph P (1983) Lactoferrin, transferrin and acidic isoferritins: Regulatory molecules with potential therapeutic value in leukemia. Blood Cells 9:83–105.

    PubMed  CAS  Google Scholar 

  6. Baggiolini M., DeDuve C., Masson PL, Heremans JF (1970) Association of lactoferrin with specific granules in rabbit heterophil leukocytes. J Exp Med 131:559–570.

    Article  PubMed  CAS  Google Scholar 

  7. Anderson B, Baker HM, Dodson E, Orris GE, Rumbail SV, Waters JM, Baker EN (1987) Structure of human lactoferrin at 3.2-Å resolution. Proc Natl Acad Sci USA 84:1769–1773.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. Broxmeyer HE, Smithyman A, Eger RR, Meyers P, DeSousa M (1978) Identification of lactoferrin as the granulocyte-derived inhibitor of colony-stimulating activity production. J Exp Med 148:1052–1067.

    Article  PubMed  CAS  Google Scholar 

  11. Broxmeyer, HE, DeSousa M., Smithyman A, Ralph, P Hamilton J, Kurland JI, Bognacki J (1980) Specificity and modulation of the action of lactoferrin, a negative feedback regulator of myelopoiesis. Blood 55:324–333.

    PubMed  CAS  Google Scholar 

  12. Bagby GC, Riga VD, Bennett RM, Van denbark AA, Garewal HS (1989) Interaction of lactoferrin, monocytes, and T-lymphocyte subsets in the regulation of steady-state granulopoiesis in vitro. J Clin Invest 68:56–63.

    Article  Google Scholar 

  13. Broxmeyer HE, Bicknell DC, Gillis S, Harris EL, Peius LM, Sledge GW (1986) Lactoferrin: Affinity purification from human milk and polymorphonuclear neutrophils using monoclonal antibody (II 2C) to human lactoferrin, development of an immunoradiometric assay using II 2C, and myelopoietic regulation and receptor-binding characters. Blood Cells 11:429–446.

    PubMed  CAS  Google Scholar 

  14. Gentile P, Broxmeyer HE (1983) Suppression of mouse myelopoiesis by administration of human lactoferrin in vivo and the comparative action of human transferrin. Blood 61:982–993.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  16. 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 

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

    PubMed  CAS  Google Scholar 

  18. Okabe-Kado J, Hayashi M, Honma Y, Hozumi M (1985) Characterization of a differentiation-inhibitory activity from non-differentiating mouse myeloid leukemia cells. Cancer Res 45:4848–4852.

    PubMed  CAS  Google Scholar 

  19. Gentile P, Broxmeyer HE (1991) Interleukin-6 ablates the accessory cell-mediated suppressive effects of lactoferrin on human hematopoietic progenitor cell proliferation in vitro. Ann NY Acad Sci 628:74–83.

    Article  PubMed  CAS  Google Scholar 

  20. Miyazawa K, Mantel C, Lu L, Morrison DC, Broxmeyer HE (1991) Lactoferrin-lipopolysaccharide interactions. Effect on lactoferrin binding to monocyte/macrophage-differentiated HL-60 cells. J Immunol 146:723–729.

    CAS  Google Scholar 

  21. Broxmeyer HE, Mendelson N, Moore MAS (1977) Abnormal granulocyte feedback of colony forming and colony stimulating activity-producing cells from patients with chronic myelogenous leukemia. Leukemia Res 1:3–12.

    Article  Google Scholar 

  22. Broxmeyer HE, Bicknell DC, Cooper S, Sledge G Jr., Williams DE, McGuire WA, Coates TD (1991) Quantitative functional deficiency of affinity-purified lactoferrin from neutrophils of patients with chronic myelogenous leukemia, and lactoferrin/H-ferritin-cell interactions in a patient with lactoferrin-deficiency with normal numbers of circulating leukocytes. Pathobiol 59:26–35.

    Article  CAS  Google Scholar 

  23. Lu L, Hangoc G, Chen LT, Shen RN, Oliff A, Broxmeyer HE (1987) The protective influence of lactoferrin on mice infected with the polycythemia-inducing strain of the Friend Virus Complex. Cancer Res 47:4184–4188.

    PubMed  CAS  Google Scholar 

  24. Lu L, Shen RN, Zhou SZ, Srivastava C., Harrington MA, Miyazawa K, Wu B, Lin ZH, Ruscetti S, Broxmeyer HE (1991) Synergistic effect of human lactoferrin and recombinant murine interferon gamma on disease progression in mice infected with the polycythemia-inducing strain of the Friend virus complex. Int J Hematol 54:117–124.

    PubMed  CAS  Google Scholar 

  25. Broxmeyer HE, Piacibello W, Juliano L, Platzer E, Berman E, Rubin BY (1986) Gamma interferon induces colony forming cells of the human monoblast cell line U937 to respond to inhibition by lactoferrin, transferrin, and acidic isoferritins. Exp Hematol 14:35–43.

    PubMed  CAS  Google Scholar 

  26. Srivastava CH, Rado TA, Bauerle D, Broxmeyer HE (1991) Regulation of human bone marrow lactoferrin and myeloperoxidase gene expression by tumor necrosis factor-α. J Immunol 146:1014–1019.

    PubMed  CAS  Google Scholar 

  27. 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 

  28. Ward PP, Lo JY, Duke M., May GS, Headon DR, Conneely OM (1992) Production of biologically active recombinant human lactoferrin in Asperigillus Oryzae. Biotechnology 10:784–789.

    Article  PubMed  CAS  Google Scholar 

  29. Bagby GC Jr, Bennett RM, Wilkinson B, Davis J (1982) Feedback regulation of granulopoiesis: polymerization of lactoferrin abrogates its ability to inhibit CSA production. Blood 60:108–112.

    PubMed  CAS  Google Scholar 

  30. Bennett RM, Bagby GC, Davis J (1981) Calcium-dependent polymerization of lactoferrin. Biochem Biophys Res Commun 101: 88–95.

    Article  PubMed  CAS  Google Scholar 

  31. Masson PL, Heremans JF (1968) Metal-combining properties of human lactoferrin (Red Milk Protein). Eur J Biochem 6: 579–584.

    Article  PubMed  CAS  Google Scholar 

  32. Bates GW, Schlabach MR (1973) The reaction of ferric salts with transferrin. J Biol. Chem 248: 3228–3232.

    PubMed  CAS  Google Scholar 

  33. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage. Nature 227: 680–685.

    Article  PubMed  CAS  Google Scholar 

  34. Legrand D, Mazurier J, Metz-Boutique M, Jolies J, Jolies P, Montreuil J, Spik G (1984) Characterization and localization of an iron-binding 18 kDa glycopeptide isolated from the N-terminal half of human lac-totransferrin. Biochim Biophys Acta 787:90–96.

    Article  PubMed  CAS  Google Scholar 

  35. Bluard-Deconinck J, Williams J, Evans RT, Van Snick J, Osinski PA, Masson PL (1978) Iron-binding fragments from the N-terminal and C-terminal regions of human lactoferrin. Biochem J 171:321–327.

    PubMed  CAS  Google Scholar 

  36. Legrand D, Mazurier J, Aubert JP, Loucheux-Lefebvre MH, Montreuil J, Spik G (1986) Evidence for interactions between the 30 KDa N-and 50 KDa C-terminal tryptic fragments of human lactotransferrin. Biochem J 236:839–844.

    PubMed  CAS  Google Scholar 

  37. Bezwoda WR, Mansoor N (1986) Isolation and characterization of lactoferrin separated from human whey by adsorption chromatography using Cibacron Blue F3G-A linked affinity adsorbent. Clin Chim Acta 157:89–94.

    Article  PubMed  CAS  Google Scholar 

  38. Rosseneu-Motreff MY, Soetewey F, Lamote R, Peeters H (1971) Size and shape determination of apotransferrin and transferrin monomers. Biopolymers 10:1039–1048.

    Article  PubMed  CAS  Google Scholar 

  39. Erlanson-Albertsson C, Sternby B, Johannesson U (1985) The interaction between pancreatic car-boxylesterhydrolase (bile-salt stimulated lipase of human milk) and lactoferrin. Biochim Biophys Acta 829:282–287.

    Article  PubMed  CAS  Google Scholar 

  40. Hekman A (1971) Association of lactoferrin with other proteins as demonstrated by changes in electrophoretic mobility. Biochim Biophys Acta 251:380–387.

    Article  PubMed  CAS  Google Scholar 

  41. Van Snick JL, Masson PL (1976) The binding of human lactoferrin to mouse peritoneal cells. J Exp Med 144:1568–1580.

    Article  PubMed  Google Scholar 

  42. Yamada Y, Amagasaki T, Jacobsen DW, Green R (1987) Lactoferrinbinding by leukemia cell lines. Blood 70:264–270.

    PubMed  CAS  Google Scholar 

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© 1994 Springer Science+Business Media New York

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Mantel, C., Miyazawa, K., Broxmeyer, H.E. (1994). Physical Characteristics and Polymerization During Iron Saturation of Lactoferrin, A Myelopoietic Regulatory Molecule with Suppressor Activity. In: Hutchens, T.W., Rumball, S.V., Lönnerdal, B. (eds) Lactoferrin. Advances in, Experimental Medicine and Biology, vol 357. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2548-6_12

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  • DOI: https://doi.org/10.1007/978-1-4615-2548-6_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6087-2

  • Online ISBN: 978-1-4615-2548-6

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