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 Bowdish, D. M. E.
Right arrow Articles by Hancock, R. E. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bowdish, D. M. E.
Right arrow Articles by Hancock, R. E. W.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2005, p. 1727-1732, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1727-1732.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Immunomodulatory Activities of Small Host Defense Peptides

Dawn M. E. Bowdish,1 Donald J. Davidson,2 Monisha G. Scott,1,3 and Robert E. W. Hancock1*

Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall Road, Vancouver, British Columbia, Canada V6T 1Z4,1 MRC Centre for Inflammation, Edinburgh University Medical School, Teviot Place, Edinburgh EH8 9AG, Scotland, United Kingdom,2 Inimex Pharmaceuticals, 2259 Lower Mall Road, Vancouver, British Columbia, Canada V6T 1Z43

Received 23 November 2004/ Returned for modification 29 November 2004/ Accepted 18 January 2005

Recent studies have demonstrated that in addition to their antimicrobial activity, cationic host defense peptides, like the human cathelicidin LL-37, perform many activities relating to innate immunity, including the induction or modulation of chemokine and cytokine production, alteration of gene expression in host cells, and inhibition of proinflammatory responses of host cells to bacterial components such as lipopolysaccharide (LPS) in vitro and in vivo. To investigate if these properties are shared by smaller peptides, two cathelicidin peptides derived from bovine neutrophils, the 13-mer indolicidin and Bac2A, a linear 12-amino-acid derivative of bactenecin, were compared to the 37-amino-acid peptide LL-37. Indolicidin, like LL-37, inhibited LPS-induced tumor necrosis factor alpha (TNF-{alpha}) secretion, even when added up to an hour after the addition of Escherichia coli O111:B4 LPS to the human macrophage/monocyte-like THP-1 cell line. In contrast, Bac2A demonstrated no significant antiendotoxin activity. At low concentrations, indolicidin and LL-37 acted synergistically to suppress LPS-induced production of TNF-{alpha}. Indolicidin was analogous to LL-37 in its ability to induce the production of the chemokine interleukin-8 (IL-8) in a human bronchial cell line, 16HBE14o–, but it was unable to induce production of IL-8 in THP-1 cells. In contrast, Bac2A was unable to induce IL-8 in either cell type. Conversely, Bac2A was chemotactic for THP-1 cells at concentrations between 10 and 100 µg/ml, while indolicidin and LL-37 were not chemotactic at these concentrations for THP-1 cells. This indicates that in addition to the potential for direct microbicidal activity, cationic host defense peptides may have diverse and complementary abilities to modulate the innate immune response.

* Corresponding author. Mailing address: Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall Road, Vancouver, British Columbia, Canada V6T 1Z4. Phone: (604) 822-2682. Fax: (604) 827-5566. E-mail: bob{at}cmdr.ubc.ca.

Antimicrobial Agents and Chemotherapy, May 2005, p. 1727-1732, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1727-1732.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kovacs-Nolan, J., Mapletoft, J. W., Lawman, Z., Babiuk, L. A., van Drunen Littel-van den Hurk, S. (2009). Formulation of bovine respiratory syncytial virus fusion protein with CpG oligodeoxynucleotide, cationic host defence peptide and polyphosphazene enhances humoral and cellular responses and induces a protective type 1 immune response in mice. J. Gen. Virol. 90: 1892-1905 [Abstract] [Full Text]  
  • Thwaite, J. E., Humphrey, S., Fox, M. A., Savage, V. L., Laws, T. R., Ulaeto, D. O., Titball, R. W., Atkins, H. S. (2009). The cationic peptide magainin II is antimicrobial for Burkholderia cepacia-complex strains. J Med Microbiol 58: 923-929 [Abstract] [Full Text]  
  • Overhage, J., Campisano, A., Bains, M., Torfs, E. C. W., Rehm, B. H. A., Hancock, R. E. W. (2008). Human Host Defense Peptide LL-37 Prevents Bacterial Biofilm Formation. Infect. Immun. 76: 4176-4182 [Abstract] [Full Text]  
  • Cheung, Q. C. K., Turner, P. V., Song, C., Wu, D., Cai, H. Y., MacInnes, J. I., Li, J. (2008). Enhanced Resistance to Bacterial Infection in Protegrin-1 Transgenic Mice. Antimicrob. Agents Chemother. 52: 1812-1819 [Abstract] [Full Text]  
  • Mookherjee, N., Wilson, H. L., Doria, S., Popowych, Y., Falsafi, R., Yu, J., Li, Y., Veatch, S., Roche, F. M., Brown, K. L., Brinkman, F. S. L., Hokamp, K., Potter, A., Babiuk, L. A., Griebel, P. J., Hancock, R. E. W. (2006). Bovine and human cathelicidin cationic host defense peptides similarly suppress transcriptional responses to bacterial lipopolysaccharide. J. Leukoc. Biol. 80: 1563-1574 [Abstract] [Full Text]  
  • Kandler, K., Shaykhiev, R., Kleemann, P., Klescz, F., Lohoff, M., Vogelmeier, C., Bals, R. (2006). The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands. Int Immunol 18: 1729-1736 [Abstract] [Full Text]  
  • Benincasa, M., Scocchi, M., Pacor, S., Tossi, A., Nobili, D., Basaglia, G., Busetti, M., Gennaro, R. (2006). Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts. J Antimicrob Chemother 58: 950-959 [Abstract] [Full Text]  
  • Dudal, S., Turriere, C., Bessoles, S., Fontes, P., Sanchez, F., Liautard, J., Liautard, J.-P., Lafont, V. (2006). Release of LL-37 by Activated Human V{gamma}9V{delta}2 T Cells: A Microbicidal Weapon against Brucella suis. J. Immunol. 177: 5533-5539 [Abstract] [Full Text]  
  • Barlow, P. G., Li, Y., Wilkinson, T. S., Bowdish, D. M. E., Lau, Y. E., Cosseau, C., Haslett, C., Simpson, A. J., Hancock, R. E. W., Davidson, D. J. (2006). The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system. J. Leukoc. Biol. 80: 509-520 [Abstract] [Full Text]  
  • Jenssen, H., Hamill, P., Hancock, R. E. W. (2006). Peptide Antimicrobial Agents. Clin. Microbiol. Rev. 19: 491-511 [Abstract] [Full Text]  
  • Thwaite, J. E., Hibbs, S., Titball, R. W., Atkins, T. P. (2006). Proteolytic Degradation of Human Antimicrobial Peptide LL-37 by Bacillus anthracis May Contribute to Virulence.. Antimicrob. Agents Chemother. 50: 2316-2322 [Abstract] [Full Text]  
  • Pochet, S., Tandel, S., Querriere, S., Tre-Hardy, M., Garcia-Marcos, M., De Lorenzi, M., Vandenbranden, M., Marino, A., Devleeschouwer, M., Dehaye, J.-P. (2006). Modulation by LL-37 of the Responses of Salivary Glands to Purinergic Agonists. Mol. Pharmacol. 69: 2037-2046 [Abstract] [Full Text]  
  • Cirioni, O., Giacometti, A., Ghiselli, R., Bergnach, C., Orlando, F., Silvestri, C., Mocchegiani, F., Licci, A., Skerlavaj, B., Rocchi, M., Saba, V., Zanetti, M., Scalise, G. (2006). LL-37 Protects Rats against Lethal Sepsis Caused by Gram-Negative Bacteria.. Antimicrob. Agents Chemother. 50: 1672-1679 [Abstract] [Full Text]  
  • Lau, Y. E., Bowdish, D. M. E., Cosseau, C., Hancock, R. E. W., Davidson, D. J. (2006). Apoptosis of Airway Epithelial Cells: Human Serum Sensitive Induction by the Cathelicidin LL-37. Am. J. Respir. Cell Mol. Bio. 34: 399-409 [Abstract] [Full Text]  
  • Mookherjee, N., Brown, K. L., Bowdish, D. M. E., Doria, S., Falsafi, R., Hokamp, K., Roche, F. M., Mu, R., Doho, G. H., Pistolic, J., Powers, J.-P., Bryan, J., Brinkman, F. S. L., Hancock, R. E. W. (2006). Modulation of the TLR-Mediated Inflammatory Response by the Endogenous Human Host Defense Peptide LL-37. J. Immunol. 176: 2455-2464 [Abstract] [Full Text]  
  • Bowdish, D. M.E., Hancock, R. E.W. (2005). Anti-endotoxin properties of cationic host defence peptides and proteins. Innate Immunity 11: 230-236 [Abstract]  


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