Biometals

, Volume 13, Issue 1, pp 15–22 | Cite as

Metal complexes of lactoferrin and their effect on the intracellular multiplication of Legionella pneumophila

  • Paola Goldoni
  • Laura Sinibaldi
  • Piera Valenti
  • Nicola Orsi
Article

Abstract

The action of bovine lactoferrin saturated with iron, zinc and manganese on the intracellular multiplication of Legionella pneumophila in HeLa cells has been tested. The results obtained showed that lactoferrin did not influence the invasive efficiency of Legionella. The intracellular multiplication of the bacterium was inhibited by apo-lactoferrin and by lactoferrin saturated with manganese and zinc, whereas lactoferrin saturated with iron enhanced the intracellular growth. Experiments in parallel were performed with iron, manganese and zinc citrate to test the effect due to the metal ions alone. Even in this condition the addition of an iron chelate enhanced the multiplication of Legionella while the manganese chelate produced a certain inhibition.

lactoferrin iron metals Legionella invasiveness 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aisen P. 1980 The Transferrins. In Jacobs A, Worwood M, eds. Iron in Biochemistry and Medicine. II. London: Academic Press; 87–129.Google Scholar
  2. Antonini G, Catania MR, Greco R et al. 1997 Anti-invasive activity of bovine lactoferrin against Listeria monocytogenes. J Food Prot 60, 267–271.Google Scholar
  3. Bortner CA, Miller RD, Arnold RR. 1986 Bactericidal effect of lactoferrin on Legionella pneumophila. Infect Immun 51, 373–377.Google Scholar
  4. Bortner CA, Arnold RR, Miller RD. 1989 Bactericidal effect of lactoferrin on Legionella pneumophila: effect of the physiological state of the organism. Can J Microbiol 35, 1048–1051.Google Scholar
  5. Byrd TF, Horwitz MA. 1989 Interferon gamma-activated human monocytes down-regulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. J Clin Invest 83, 1457–1465.Google Scholar
  6. Byrd TF, Horwitz MA. 1991a Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens. J Clin Invest 88, 351–357.Google Scholar
  7. Byrd TF, Horwitz MA. 1991b Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila. J Clin Invest 88, 1103–1112.Google Scholar
  8. Byrd TF, Horwitz MA. 1993 Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes: coordinate upregulation by iron-transferrin and down-regulation by interferon gamma. J Clin Invest 91, 969–976.Google Scholar
  9. Cattani L, Goldoni P, Castellani Pastoris M, Sinibaldi L, Orsi N. 1997 Bafilomycin A1 and intracellular multiplication of Legionella pneumophila. Antimicrob Agents Chemother 41, 212–214.Google Scholar
  10. Chasteen ND, Woodworth RC. 1990 Transferrin and lactoferrin. In Ponka P, Shulman HM, Woodworth RC eds. Iron Transport and Storage. Boston: CRC Press; 67–69.Google Scholar
  11. Fields BS. 1993Legionella and protozoa: interaction of a pathogen and its natural host. In Barbaree JM, Breiman RF, Dufour AP eds. Legionella Current Status and Emerging Perspectives. Washington D.C.: American Society for Microbiology; 129–136.Google Scholar
  12. Finlay BB, Falkow S. 1988 Comparison of the invasion strategies used by Salmonella cholerae-suis, Shigella flexneri and Yersinia enterocolitica to enter cultured animal cells: endosome acidification is not required for bacterial invasion or intracellular replication. Biochimie 70, 1089–1099.Google Scholar
  13. Furuchi T, Aikawa K, Arai H, Inoue K. 1993 Bafilomycin A1, a specific inhibitor of vacuolar-type HC-ATPase, blocks lysosomal cholesterol trafficking in macrophages. J Biol Chem 268, 27354–27348.Google Scholar
  14. Goldoni P, Visca P, Castellani Pastoris M, Valenti P, Orsi N. 1991 Growth of Legionella under conditions of iron restriction. J Med Microbiol 34, 113–118.Google Scholar
  15. Goldoni P, Castellani Pastoris M, Cattani L, Peluso C, Sinibaldi L, Orsi N. 1995 Effect of monensin on the invasiveness and multiplication of Legionella pneumophila. J Med Microbiol 42, 269–275.Google Scholar
  16. Green GM, Byrd TF. 1997 The immune response to Legionella infection. In Kaufmann SHE ed. Medical Intelligence Unit. Host response to intracellular pathogens. Heidelberg: Springer-Verlag; 97–114.Google Scholar
  17. Harley VS, Drasar BS, Forrest B, Krahn B, Tovey G. 1989 Invasion strategies and intracellular growth of bacterial pathogens. Biochem Soc Trans 17, 1118 (631st Meeting, Guildford).Google Scholar
  18. Horwitz MA. 1993 Toward an understanding of host and bacterial molecules mediating Legionella pneumophila pathogenesis. In Barbaree JM, Breiman RF, Dufour AP, eds. Legionella Current Status and Emerging Perspectives. Washington D.C.: American Society for Microbiology; 55–62.Google Scholar
  19. Longhi C, Conte MP, Seganti L, Polidoro M, Alfsen A, Valenti P. 1993 Influence of lactoferrin on the entry process of Escherichia coli HB101(pRI203) in HeLa cells. Med Microbiol Immunol 182, 25–35.Google Scholar
  20. Manabe T, Yoshimori T, Henomatsu N, Tashiro Y. 1993 Inhibitors of vacuolar-type HC-ATPase suppresses proliferation of cultured cells. J Cell Physiol 157, 445–452.Google Scholar
  21. Maxfield FR. 1982 Weak bases and ionophores rapidly and reversibly raise the pH of endocytic vesicles in cultured mouse fibroblasts. J Cell Biol 95, 676–681.Google Scholar
  22. Moguilewsky N, Massan PL, Courtoy PJ. 1987 Lactoferrin uptake and iron processing into macrophages: a study in familial hemochromatosis. Br J Haematol 66, 129–136.Google Scholar
  23. Oldham LJ, Rodgers FG. 1985 Adhesion, penetration and intracellular replication of Legionella pneumophila: an in vitro model of pathogenesis. J Gen Microbiol 131, 697–706.Google Scholar
  24. Quinn FD, Weinberg ED. 1988 Killing of Legionella pneumophila by human serum and iron-binding agents. Curr Microbiol 17, 111–116.Google Scholar
  25. Reeves MW, Pine LP, Hutner SH, George JB, Knox Harrele W. 1981 Metal requirements of Legionella pneumophila. J Clin Microbiol 13, 688–695.Google Scholar
  26. Reeves MW, Pine LP, Neilands JB, Balows A. 1983 Absence of siderophore activity in Legionella species grown in iron deficient media. J Bacteriol 154, 324–329.Google Scholar
  27. Shuman HA, Horwitz MA. 1996 Legionella pneumophila invasion of mononuclear phagocytes. In Virginia L Miller, ed. Bacterial Invasiveness. Heidelberg: Springer-Verlag; 99–112.Google Scholar
  28. Tartakoff AM. 1983 Perturbation of vesicular traffic with the carboxylic ionophore monensin. Cell 32, 1026–1028.Google Scholar
  29. Valenti P, Visca P, Antonini G, Orsi N, Antonini E. 1987 The effect of saturation with Zn2C and other metal ions on the antibacterial activity of ovotransferrin. Med Microbiol Immunol 176, 123–130.Google Scholar
  30. Wu HF, Monroe DM, Church FC. 1995 Characterization of the glycosaminoglycan binding region of lactoferrin. Arch Biochem Biophys 317, 85–92.Google Scholar
  31. Yoshimori TA, Yamamoto A, Moriyama Y, Futai M, Tashiro Y. 1991 Bafilomycin A1, a specific inhibitor of vacuolat-type HC-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem 266, 17707–17712.Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Paola Goldoni
  • Laura Sinibaldi
  • Piera Valenti
  • Nicola Orsi

There are no affiliations available

Personalised recommendations