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 Cavalcante, I. C.
Right arrow Articles by Brito, G. A. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cavalcante, I. C.
Right arrow Articles by Brito, G. A. C.

 Previous Article  |  Next Article 

Infection and Immunity, May 2006, p. 2606-2612, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2606-2612.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Effect of Novel A2A Adenosine Receptor Agonist ATL 313 on Clostridium difficile Toxin A-Induced Murine Ileal Enteritis

I. C. Cavalcante,1 M. V. Castro,1 A. R. F. Barreto,1 G. W. Sullivan,2 M. Vale,1 P. R. C. Almeida,1 J. Linden,2 J. M. Rieger,3 F. Q. Cunha,4 R. L. Guerrant,2 R. A. Ribeiro,1 and G. A. C. Brito1*

Faculty of Medicine, Federal University of Ceará, Ceará, Brazil,1 University of Virginia,2 Adenosine Therapeutics, LLC, Charlottesville, Virginia,3 Faculty of Medicine of Ribeirão Preto, São Paulo University, São Paulo, Brazil4

Received 4 December 2005/ Returned for modification 6 January 2006/ Accepted 12 February 2006

Clostridium difficile is a spore-forming, anaerobic, gram-positive bacillus that releases two main virulence factors: toxins A and B. Toxin A plays an important pathogenic role in antibiotic-induced diarrhea and pseudomembranous colitis, a condition characterized by intense mucosal inflammation and secretion. Agonist activity at A2A adenosine receptors attenuates inflammation and damage in many tissues. This study evaluated the effects of a new selective A2A adenosine receptor agonist (ATL 313) on toxin A-induced injury in murine ileal loops. ATL 313 (0.5 to 5 nM) and/or the A2A adenosine receptor antagonist (ZM241385; 5 nM) or phosphate-buffered saline (PBS) were injected into ileal loops immediately prior to challenge with toxin A (1 to 10 µg/loop) or PBS. Intestinal fluid volume/length and weight/length ratios were calculated 3 h later. Ileal tissues were collected for the measurement of myeloperoxidase, adenosine deaminase activity, tumor necrosis factor alpha (TNF-{alpha}) production, histopathology, and detection of cell death by the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) method. Toxin A significantly increased volume/length and weight/length ratios in a dose-dependent fashion. ATL 313 treatment significantly (P < 0.05) reduced toxin A-induced secretion and edema, prevented mucosal disruption, and neutrophil infiltration as measured by myeloperoxidase activity. ATL 313 also reduced the toxin A-induced TNF-{alpha} production and adenosine deaminase activity and prevented toxin A-induced cell death. These protective effects of ATL 313 were reversed by ZM241385. In conclusion, the A2A adenosine receptor agonist, ATL 313, reduces tissue injury and inflammation in mice with toxin A-induced enteritis. The finding of increased ileal adenosine deaminase activity following the administration of toxin A is new and might contribute to the pathogenesis of the toxin A-induced enteritis by deaminating endogenous adenosine.

* Corresponding author. Mailing address: Departamento de Morfologia, Faculdade de Medicina, Universidade Federal do Ceará, Rua Delmiro de Farias, sn CEP 60.416-030, Fortaleza, CE, Brazil. Phone: 55 85 4009 8588. Fax: 55 85 4009 8333. E-mail: gerlybrito{at}hotmail.com.

Editor: J. T. Barbieri

Infection and Immunity, May 2006, p. 2606-2612, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2606-2612.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nakav, S., Naamani, O., Chaimovitz, C., Shaked, G., Czeiger, D., Zlotnik, M., Douvdevani, A. (2009). Regulation of adenosine system at the onset of peritonitis. Nephrol Dial Transplant 0: gfp542v1-gfp542 [Abstract] [Full Text]  
  • (2009). From the Cover: CD39 deletion exacerbates experimental murine colitis and human polymorphisms increase susceptibility to inflammatory bowel disease. Proc. Natl. Acad. Sci. USA 106: 16788-16793  
  • Frick, J.-S., MacManus, C. F., Scully, M., Glover, L. E., Eltzschig, H. K., Colgan, S. P. (2009). Contribution of Adenosine A2B Receptors to Inflammatory Parameters of Experimental Colitis. J. Immunol. 182: 4957-4964 [Abstract] [Full Text]  
  • Louis, N. A., Robinson, A. M., MacManus, C. F., Karhausen, J., Scully, M., Colgan, S. P. (2008). Control of IFN-{alpha}A by CD73: Implications for Mucosal Inflammation. J. Immunol. 180: 4246-4255 [Abstract] [Full Text]  
  • Kolachala, V. L., Bajaj, R., Chalasani, M., Sitaraman, S. V. (2008). Purinergic receptors in gastrointestinal inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 294: G401-G410 [Abstract] [Full Text]  
  • Antonioli, L., Fornai, M., Colucci, R., Ghisu, N., Da Settimo, F., Natale, G., Kastsiuchenka, O., Duranti, E., Virdis, A., Vassalle, C., La Motta, C., Mugnaini, L., Breschi, M. C., Blandizzi, C., Del Taca, M. (2007). Inhibition of Adenosine Deaminase Attenuates Inflammation in Experimental Colitis. J. Pharmacol. Exp. Ther. 322: 435-442 [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»