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 Sawa, T.
Right arrow Articles by Wiener-Kronish, J. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sawa, T.
Right arrow Articles by Wiener-Kronish, J. P.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 1998, p. 3269-3275, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Evaluation of Antimicrobial and Lipopolysaccharide-Neutralizing Effects of a Synthetic CAP18 Fragment against Pseudomonas aeruginosa in a Mouse Model

Teiji Sawa,1 Kiyoyasu Kurahashi,1 Maria Ohara,1 Michael A. Gropper,1 Vatsal Doshi,1 James W. Larrick,2 and Jeanine P. Wiener-Kronish1,*

Departments of Anesthesia and Medicine, The University of California, San Francisco, California 94143,1 and Palo Alto Institute of Molecular Medicine, Mountain View, California 940432

Received 28 May 1998/Returned for modification 6 August 1998/Accepted 12 September 1998

CAP18 (cationic antimicrobial protein; 18 kDa) is a neutrophil-derived protein that can bind to and inhibit various activities of lipopolysaccharide (LPS). The 37 C-terminal amino acids of CAP18 make up the LPS-binding domain. A truncated 32-amino-acid C-terminal fragment of CAP18 had potent activity against Pseudomonas aeruginosa in vitro. We studied the antimicrobial and LPS-neutralizing effects of this synthetic truncated CAP18 peptide (CAP18106-137) on lung injury in mice infected with cytotoxic P. aeruginosa. To determine its maximal effect, the CAP18106-137 peptide was mixed with bacteria just prior to tracheal instillation, and lung injury was evaluated by determining the amount of leakage of an alveolar protein tracer (125I-albumin) into the circulation and by the quantification of lung edema. The lung injury caused by the instillation of 5 × 105 CFU of P. aeruginosa was significantly reduced by the concomitant instillation of CAP18106-137. However, the administration of CAP18106-137 alone, without bacteria, induced lung edema, suggesting that it has some toxicity. Also, the peptide did not significantly reduce the number of bacteria that had been simultaneously instilled, nor did it significantly improve the survival of the infected mice. The addition of CAP18106-137 to aztreonam along with the bacteria did decrease the level of antibiotic-induced release of inflammatory mediators including tumor necrosis factor alpha, interleukin-6, and nitric oxide and also improved the survival of the mice. Therefore, more investigations are needed to confirm the toxicities and the therapeutic benefits of CAP18106-137 as an adjunctive therapy to antibiotics in the treatment of infections caused by gram-negative bacteria.

* Corresponding author. Mailing address: Departments of Anesthesia and Medicine, The University of California, San Francisco, CA 94143. Phone: (415) 476-8968. Fax: (415) 476-8841. E-mail: jwk{at}jemo.ucsf.edu.

Antimicrobial Agents and Chemotherapy, December 1998, p. 3269-3275, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Augustin, D. K., Song, Y., Baek, M. S., Sawa, Y., Singh, G., Taylor, B., Rubio-Mills, A., Flanagan, J. L., Wiener-Kronish, J. P., Lynch, S. V. (2007). Presence or Absence of Lipopolysaccharide O Antigens Affects Type III Secretion by Pseudomonas aeruginosa. J. Bacteriol. 189: 2203-2209 [Abstract] [Full Text]  
  • Andra, J., Gutsmann, T., Garidel, P., Brandenburg, K. (2006). Invited review: Mechanisms of endotoxin neutralization by synthetic cationic compounds. Innate Immunity 12: 261-277 [Abstract]  
  • Okuda, D., Yomogida, S., Tamura, H., Nagaoka, I. (2006). Determination of the Antibacterial and Lipopolysaccharide-Neutralizing Regions of Guinea Pig Neutrophil Cathelicidin Peptide CAP11.. Antimicrob. Agents Chemother. 50: 2602-2607 [Abstract] [Full Text]  
  • Bowdish, D. M. E., Davidson, D. J., Lau, Y. E., Lee, K., Scott, M. G., Hancock, R. E. W. (2005). Impact of LL-37 on anti-infective immunity. J. Leukoc. Biol. 77: 451-459 [Abstract] [Full Text]  
  • Levy, O. (2004). Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes. J. Leukoc. Biol. 76: 909-925 [Abstract] [Full Text]  
  • Kurahashi, K., Ota, S., Nakamura, K., Nagashima, Y., Yazawa, T., Satoh, M., Fujita, A., Kamiya, R., Fujita, E., Baba, Y., Uchida, K., Morimura, N., Andoh, T., Yamada, Y. (2004). Effect of lung-protective ventilation on severe Pseudomonas aeruginosa pneumonia and sepsis in rats. Am. J. Physiol. Lung Cell. Mol. Physiol. 287: L402-L410 [Abstract] [Full Text]  
  • Bartlett, K. H., McCray, P. B. Jr., Thorne, P. S. (2003). Novispirin G10-Induced Lung Toxicity in a Klebsiella pneumoniae Infection Model. Antimicrob. Agents Chemother. 47: 3901-3906 [Abstract] [Full Text]  
  • Nagaoka, I., Hirota, S., Niyonsaba, F., Hirata, M., Adachi, Y., Tamura, H., Tanaka, S., Heumann, D. (2002). Augmentation of the Lipopolysaccharide-Neutralizing Activities of Human Cathelicidin CAP18/LL-37-Derived Antimicrobial Peptides by Replacement with Hydrophobic and Cationic Amino Acid Residues. CVI 9: 972-982 [Abstract] [Full Text]  
  • Nir-Paz, R., Prevost, M.-C., Nicolas, P., Blanchard, A., Wroblewski, H. (2002). Susceptibilities of Mycoplasma fermentans and Mycoplasma hyorhinis to Membrane-Active Peptides and Enrofloxacin in Human Tissue Cell Cultures. Antimicrob. Agents Chemother. 46: 1218-1225 [Abstract] [Full Text]  
  • Yau, Y. H., Ho, B., Tan, N. S., Ng, M. L., Ding, J. L. (2001). High Therapeutic Index of Factor C Sushi Peptides: Potent Antimicrobials against Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 45: 2820-2825 [Abstract] [Full Text]  
  • Brogden, K. A., Kalfa, V. C., Ackermann, M. R., Palmquist, D. E., McCray, P. B. Jr., Tack, B. F. (2001). The Ovine Cathelicidin SMAP29 Kills Ovine Respiratory Pathogens In Vitro and in an Ovine Model of Pulmonary Infection. Antimicrob. Agents Chemother. 45: 331-334 [Abstract] [Full Text]  
  • CRAPO, J. D., HARMSEN, A. G., SHERMAN, M. P., MUSSON, R. A. (2000). Pulmonary Immunobiology and Inflammation in Pulmonary Diseases. Am. J. Respir. Crit. Care Med. 162: 1983-1986 [Full Text]  
  • Levy, O. (2000). Antimicrobial proteins and peptides of blood: templates for novel antimicrobial agents. Blood 96: 2664-2672 [Abstract] [Full Text]  
  • Ernst, E. J., Hashimoto, S., Guglielmo, J., Sawa, T., Pittet, J.-F., Kropp, H., Jackson, J. J., Wiener-Kronish, J. P. (1999). Effects of Antibiotic Therapy on Pseudomonas aeruginosa-Induced Lung Injury in a Rat Model. Antimicrob. Agents Chemother. 43: 2389-2394 [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»