Bacterial-induced hepoxilin A3 secretion as a pro-inflammatory mediator.
Bacterial infections at epithelial surfaces, such as those that line the gut and the lung, stimulate the migration of neutrophils through the co-ordinated actions of chemoattractants secreted from pathogen-stimulated epithelial cells. One such factor involved in attracting polymorphonuclear leukocytes across the epithelium and into the lumen has until recently remained elusive. In 2004, we identified the eicosanoid, hepoxilin A(3), to be selectively secreted from the apical surface of human intestinal or lung epithelial cells stimulated with Salmonella enterica serotype Typhimurium or Pseudomonas aeruginosa, respectively. In this role, the function of hepoxilin A(3) is to guide neutrophils, via the establishment of a gradient, across the epithelial tight junction complex. Interestingly, interruption of the synthetic pathway of hepoxilin A(3) blocks the apical release of hepoxilin A(3)in vitro and the transmigration of neutrophils induced by S. typhimurium both in in vitro and in vivo models of inflammation. Such results have led to the discovery of a completely novel pathway that is not only critical for responses to bacterial pathogens but also has broad implications for inflammatory responses affecting mucosal surfaces in general. Thus, the objective of this review was to highlight the recent findings that implicate hepoxilin A(3) as a key regulator of mucosal inflammation.
McCormick
Beth A
BA
Department of Pediatric Gastroenterology, Massachusetts General Hospital, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Charlestown, MA, USA.
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002633:Chemotaxis; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism
D001095:Arachidonic Acids; D018836:Inflammation Mediators; C038243:8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid; D015126:8,11,14-Eicosatrienoic Acid