This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00407-08v1 76/8/3614    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Mumy, K. L. Articles by McCormick, B. A. PubMed PubMed Citation Articles by Mumy, K. L. Articles by McCormick, B. A.

 Previous Article  |  Next Article 

Infection and Immunity, August 2008, p. 3614-3627, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00407-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Distinct Isoforms of Phospholipase A₂ Mediate the Ability of Salmonella enterica Serotype Typhimurium and Shigella flexneri To Induce the Transepithelial Migration of Neutrophils

Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts,¹ The Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts,² The University of California, Berkeley, Center for Eye Disease and Development School of Optometry, Berkeley, California³

Received 1 April 2008/ Returned for modification 6 May 2008/ Accepted 19 May 2008

Salmonella spp. and Shigella spp. are responsible for millions of cases of enteric disease each year worldwide. While these pathogens have evolved distinct strategies for interacting with the human intestinal epithelium, they both induce significant proinflammatory responses that result in massive transepithelial migration of neutrophils across the intestinal mucosa. It has previously been shown with Salmonella enterica serotype Typhimurium that the process of neutrophil transmigration is mediated in part by the secretion of hepoxilin A₃ (HXA₃; 8-hydroxy-11,12-epoxy-eicosatetraenoic acid), a potent neutrophil chemoattractant, from the apical surface of infected model intestinal epithelium. This study confirms that HXA₃ is also secreted in response to infection by Shigella flexneri, that it is produced by a pathway involving 12/15-lipoxygenase (12/15-LOX), and that S. enterica serovar Typhimurium and S. flexneri share certain elements in the mechanism(s) that underlies the otherwise separate signal transduction pathways that are engaged to induce polymorphonuclear leukocyte (PMN) transepithelial migration (protein kinase C and extracellular signal-regulated kinases 1 and 2, respectively). PMN transepithelial migration in response to infection with S. flexneri was dependent on 12/15-LOX activity, the enzyme responsible for the initial metabolism of arachidonic acid to HXA₃. Probing further into this pathway, we also found that S. enterica serovar Typhimurium and S. flexneri activate different subtypes of phospholipase A₂, a critical enzyme involved in the liberation of arachidonic acid from cellular membranes. Thus, although S. enterica serovar Typhimurium and S. flexneri utilize different mechanisms for triggering the induction of PMN transepithelial migration, we found that their reliance on 12/15-LOX is conserved, suggesting that enteric pathogens may ultimately stimulate similar pathways for the synthesis and release of HXA₃.

Published ahead of print on 27 May 2008.

Editor: J. B. Bliska