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 Calderón, G. M.
Right arrow Articles by Enciso, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Calderón, G. M.
Right arrow Articles by Enciso, J. A.

 Previous Article  |  Next Article 

Infect Immun, June 1998, p. 2755-2761, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Effects of Toxin A from Clostridium difficile on Mast Cell Activation and Survival

Gloria M. Calderón,1 Javier Torres-López,1 Tong-Jun Lin,2 Bibiana Chavez,3 Manuel Hernández,4 Onofre Muñoz,1 A. Dean Befus,2 and J. Antonio Enciso1,*

UIMEIP, Hospital de Pediatría, CMN Siglo XXI, IMSS, México City,1 and Departamento de Patología Experimental3 and Departamento de Biología Celular,4 CINVESTAV, IPN México City, México, and PRG, University of Alberta, Edmonton, Alberta, Canada2

Received 11 December 1997/Returned for modification 2 February 1998/Accepted 11 March 1998

Toxins A and B from Clostridium difficile are the main cause of antibiotic-associated diarrhea and pseudomembranous colitis. They cause fluid accumulation, necrosis, and a strong inflammatory response when inoculated in intestinal loops. Since mast cells are a rich source of inflammatory mediators, abundant in the gut, and known to be involved in C. difficile-induced enteritis, we studied the in vitro effect of toxin A on isolated mast cells. Normal rats sensitized by infection with Nippostrongilus brasiliensis were used to isolate peritoneal mast cells (PMC). PMC from naive rats were stimulated with calcium ionophore A23187 as a model of antigen-independent activation, and PMC from sensitized rats were stimulated with N. brasiliensis antigens to study immunoglobulin E-dependent mast cell activation. After 4 h, toxin A did not induce release of nitric oxide or histamine in naive PMC. However, 10 ng of toxin per ml caused a significant release of tumor necrosis factor alpha (TNF-alpha ). In contrast, 1 µg of toxin per ml inhibited antigen or A23187-induced histamine release by PMC. Toxin A at 1 µg/ml for 4 h caused disruption of actin which aggregated in the cytoplasm and around the nucleus. After 24 h, chromatin condensation, cytoplasmic blebbing, and apoptotic-like vesicles were observed; DNA fragmentation was documented also. These results suggest that mast cells may participate in the initial inflammatory response to C. difficile infection by releasing TNF-alpha upon interaction with toxin A. However, longer exposure to toxin A affects the release of inflammatory mediators, perhaps because of the alteration of the cytoskeleton and induction of apoptosis. The impaired functions and survival of mast cells by C. difficile toxin A could hamper the capacity of these cells to counteract the infection, thus prolonging the pathogenic effects of C. difficile toxins.

* Corresponding author. Mailing address: Hospital de Pediatría, CMN Siglo XXI, Av. Cuauhtémoc 330 Col Doctores, México 06725, D.F., Mexico. Phone: (525) 627-69-40. Fax: (525) 627-69-49. E-mail: enciso{at}buzón.main.conacyt.mx.

Infect Immun, June 1998, p. 2755-2761, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Meyer, G. K. A., Neetz, A., Brandes, G., Tsikas, D., Butterfield, J. H., Just, I., Gerhard, R. (2007). Clostridium difficile Toxins A and B Directly Stimulate Human Mast Cells. Infect. Immun. 75: 3868-3876 [Abstract] [Full Text]  
  • Jenkins, C. E., Swiatoniowski, A., Power, M. R., Lin, T.-J. (2006). Pseudomonas aeruginosa-Induced Human Mast Cell Apoptosis Is Associated with Up-Regulation of Endogenous Bcl-xS and Down-Regulation of Bcl-xL. J. Immunol. 177: 8000-8007 [Abstract] [Full Text]  
  • Chae, S., Eckmann, L., Miyamoto, Y., Pothoulakis, C., Karin, M., Kagnoff, M. F. (2006). Epithelial Cell I{kappa}B-Kinase beta Has an Important Protective Role in Clostridium difficile Toxin A-Induced Mucosal Injury. J. Immunol. 177: 1214-1220 [Abstract] [Full Text]  
  • Cavalcante, I. C., Castro, M. V., Barreto, A. R. F., Sullivan, G. W., Vale, M., Almeida, P. R. C., Linden, J., Rieger, J. M., Cunha, F. Q., Guerrant, R. L., Ribeiro, R. A., Brito, G. A. C. (2006). Effect of Novel A2A Adenosine Receptor Agonist ATL 313 on Clostridium difficile Toxin A-Induced Murine Ileal Enteritis.. Infect. Immun. 74: 2606-2612 [Abstract] [Full Text]  
  • Carneiro, B. A., Fujii, J., Brito, G. A. C., Alcantara, C., Oria, R. B., Lima, A. A. M., Obrig, T., Guerrant, R. L. (2006). Caspase and Bid Involvement in Clostridium difficile Toxin A-Induced Apoptosis and Modulation of Toxin A Effects by Glutamine and Alanyl-Glutamine In Vivo and In Vitro. Infect. Immun. 74: 81-87 [Abstract] [Full Text]  
  • Voth, D. E., Ballard, J. D. (2005). Clostridium difficile Toxins: Mechanism of Action and Role in Disease. Clin. Microbiol. Rev. 18: 247-263 [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»