This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, G.-H.
Right arrow Articles by Tsai, C.-M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, G.-H.
Right arrow Articles by Tsai, C.-M.

 Previous Article  |  Next Article 

Infection and Immunity, March 1999, p. 1353-1358, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Neutralization of Endotoxin In Vitro and In Vivo by a Human Lactoferrin-Derived Peptide

Gui-Hang Zhang,1,* David M. Mann,2,3 and Chao-Ming Tsai1

Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 208521; J. H. Holland Laboratory, Plasma Derivatives Department, American Red Cross, Rockville, Maryland 208552; and Department of Biochemistry and Molecular Biology and the Institute for Biochemical Sciences, George Washington University Medical Center, Washington, D.C. 200373

Received 31 July 1998/Returned for modification 28 September 1998/Accepted 11 December 1998

Endotoxin (lipopolysaccharide [LPS]) is the major pathogenic factor of gram-negative septic shock, and endotoxin-induced death is associated with the host overproduction of tumor necrosis factor alpha (TNF-alpha ). In the search for new antiendotoxin molecules, we studied the endotoxin-neutralizing capacity of a human lactoferrin-derived 33-mer synthetic peptide (GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGP; designated LF-33) representing the minimal sequence for lactoferrin binding to glycosaminoglycans. LF-33 inhibited the coagulation of the Limulus amebocyte lysate and the secretion of TNF-alpha by RAW 264.7 cells induced by lipid A and four different endotoxins with a potency comparable to that of polymyxin B. The first six residues at the N terminus of LF-33 were critical for its antiendotoxin activity. The endotoxin-neutralizing capacity of LF-33 and polymyxin B was attenuated by human serum. Coinjection of Escherichia coli LPS (125 ng) with LF-33 (2.5 µg) dramatically reduced the lethality of LPS in the galactosamine-sensitized mouse model. Significant protection of the mice against the lethal LPS challenge was also observed when LF-33 (100 µg) was given intravenously after intraperitoneal injection of LPS. Protection was correlated with a reduction in TNF-alpha levels in the mouse serum. These results demonstrate the endotoxin-neutralizing capability of LF-33 in vitro and in vivo and its potential use for the treatment of endotoxin-induced septic shock.

* Corresponding author. Mailing address: Plasma Derivatives Department, J. H. Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855. Phone: (301) 738-0545. Fax: (301) 738-0794. E-mail: zhanggu{at}usa.redcross.org.

Infection and Immunity, March 1999, p. 1353-1358, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Hunter, H. N., Demcoe, A. R., Jenssen, H., Gutteberg, T. J., Vogel, H. J. (2005). Human Lactoferricin Is Partially Folded in Aqueous Solution and Is Better Stabilized in a Membrane Mimetic Solvent. Antimicrob. Agents Chemother. 49: 3387-3395 [Abstract] [Full Text]  
  • McMichael, J. W., Roghanian, A., Jiang, L., Ramage, R., Sallenave, J.-M. (2005). The Antimicrobial Antiproteinase Elafin Binds to Lipopolysaccharide and Modulates Macrophage Responses. Am. J. Respir. Cell Mol. Bio. 32: 443-452 [Abstract] [Full Text]  
  • Santamaria, C., Larios, S., Quiros, S., Pizarro-Cerda, J., Gorvel, J.-P., Lomonte, B., Moreno, E. (2005). Bactericidal and Antiendotoxic Properties of Short Cationic Peptides Derived from a Snake Venom Lys49 Phospholipase A2. Antimicrob. Agents Chemother. 49: 1340-1345 [Abstract] [Full Text]  
  • Silverstein, R. (2004). Review: D-Galactosamine lethality model: scope and limitations. Innate Immunity 10: 147-162 [Abstract]  
  • Andra, J., Koch, M. H. J., Bartels, R., Brandenburg, K. (2004). Biophysical Characterization of Endotoxin Inactivation by NK-2, an Antimicrobial Peptide Derived from Mammalian NK-Lysin. Antimicrob. Agents Chemother. 48: 1593-1599 [Abstract] [Full Text]  
  • 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. Infect. Immun. 71: 5149-5155 [Abstract] [Full Text]  
  • Van Amersfoort, E. S., Van Berkel, T. J. C., Kuiper, J. (2003). Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock. Clin. Microbiol. Rev. 16: 379-414 [Abstract] [Full Text]  
  • Caccavo, D., Pellegrino, N. M., Altamura, M., Rigon, A., Amati, L., Amoroso, A., Jirillo, E. (2002). Review: Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application. Innate Immunity 8: 403-417 [Abstract]  
  • 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. Biol. Reprod. 67: 1439-1449 [Abstract] [Full Text]  
  • Scott, M. G., Davidson, D. J., Gold, M. R., Bowdish, D., Hancock, R. E. W. (2002). The Human Antimicrobial Peptide LL-37 Is a Multifunctional Modulator of Innate Immune Responses. J. Immunol. 169: 3883-3891 [Abstract] [Full Text]  
  • Kim, H. S., Cho, J. H., Park, H. W., Yoon, H., Kim, M. S., Kim, S. C. (2002). Endotoxin-Neutralizing Antimicrobial Proteins of the Human Placenta. J. Immunol. 168: 2356-2364 [Abstract] [Full Text]  
  • Nibbering, P. H., Ravensbergen, E., Welling, M. M., van Berkel, L. A., van Berkel, P. H. C., Pauwels, E. K. J., Nuijens, J. H. (2001). Human Lactoferrin and Peptides Derived from Its N Terminus Are Highly Effective against Infections with Antibiotic-Resistant Bacteria. Infect. Immun. 69: 1469-1476 [Abstract] [Full Text]  
  • Lupetti, A., Paulusma-Annema, A., Welling, M. M., Senesi, S., van Dissel, J. T., Nibbering, P. H. (2000). Candidacidal Activities of Human Lactoferrin Peptides Derived from the N Terminus. Antimicrob. Agents Chemother. 44: 3257-3263 [Abstract] [Full Text]  
  • Cirioni, O., Giacometti, A., Barchiesi, F., Scalise, G. (2000). Inhibition of growth of Pneumocystis carinii by lactoferrins alone and in combination with pyrimethamine, clarithromycin and minocycline. J Antimicrob Chemother 46: 577-582 [Abstract] [Full Text]  
  • Scott, M. G., Rosenberger, C. M., Gold, M. R., Finlay, B. B., Hancock, R. E. W. (2000). An {alpha}-Helical Cationic Antimicrobial Peptide Selectively Modulates Macrophage Responses to Lipopolysaccharide and Directly Alters Macrophage Gene Expression. J. Immunol. 165: 3358-3365 [Abstract] [Full Text]  
  • TAN, N. S., HO, B., DING, J. L. (2000). High-affinity LPS binding domain(s) in recombinant factor C of a horseshoe crab neutralizes LPS-induced lethality. FASEB J. 14: 859-870 [Abstract] [Full Text]  
  • Iwagaki, A., Porro, M., Pollack, M. (2000). Influence of Synthetic Antiendotoxin Peptides on Lipopolysaccharide (LPS) Recognition and LPS-Induced Proinflammatory Cytokine Responses by Cells Expressing Membrane-Bound CD14. Infect. Immun. 68: 1655-1663 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»