Open AccessDistinct Isoforms of Phospholipase A 2 Mediate the Ability of Salmonella enterica Serotype Typhimurium and Shigella flexneri To Induce the Transepithelial Migration of Neutrophils
Author(s) -
Karen L. Mumy,
Jeffrey D. Bien,
Michael A. Pazos,
Karsten Gronert,
Bryan P. Hurley,
Beth A. McCormick
Publication year - 2008
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00407-08
Subject(s) - shigella flexneri , salmonella enterica , biology , microbiology and biotechnology , intestinal epithelium , proinflammatory cytokine , intestinal mucosa , salmonella , epithelium , immunology , biochemistry , inflammation , bacteria , escherichia coli , medicine , genetics , gene
Salmonella spp. andShigella 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 withSalmonella 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 byShigella flexneri , that it is produced by a pathway involving 12/15-lipoxygenase (12/15-LOX), and thatS. enterica serovar Typhimurium andS. 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 withS. 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 thatS. enterica serovar Typhimurium andS. flexneri activate different subtypes of phospholipase A2 , a critical enzyme involved in the liberation of arachidonic acid from cellular membranes. Thus, althoughS. enterica serovar Typhimurium andS. 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 .