Identification of hepoxilin A3 in inflammatory events: a required role in neutrophil migration across intestinal epithelia
| Autor: | Bryan P. Hurley, Tor C. Savidge, Beth A. McCormick, James L. Madara, Randall J. Mrsny, Andrew T. Gewirtz, Dario Siccardi |
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| Rok vydání: | 2004 |
| Předmět: |
Inflammation
Salmonella typhimurium Multidisciplinary Tight junction Neutrophils Chemotaxis Biology Biological Sciences Transepithelial Migration Cell biology chemistry.chemical_compound 8 11 14-Eicosatrienoic Acid chemistry Eicosanoid Intestinal mucosa Hepoxilin Immunology medicine Humans medicine.symptom Intestinal Mucosa Electrochemical gradient |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 101(19) |
| ISSN: | 0027-8424 |
| Popis: | The mechanism by which neutrophils [polymorphonuclear leukocyte (PMNs)] are stimulated to move across epithelial barriers at mucosal surfaces has been basically unknown in biology. IL-8 has been shown to stimulate PMNs to leave the bloodstream at a local site of mucosal inflammation, but the chemical gradient used by PMNs to move between adjacent epithelial cells and traverse the tight junction at the apical neck of these mucosal barriers has eluded identification. Our studies not only identify this factor, previously termed pathogen-elicited epithelial chemoattractant, as the eicosanoid hepoxilin A3(hepA3) but also demonstrate that it is a key factor promoting the final step in PMN recruitment to sites of mucosal inflammation. We show that hepA3is synthesized by epithelial cells and secreted from their apical surface in response to conditions that stimulate inflammatory events. Our data further establish that hepA3acts to draw PMNs, via the establishment of a gradient across the epithelial tight junction complex. The functional significance of hepA3to target PMNs to the lumen of the gut at sites of inflammation was demonstrated by the finding that disruption of the 12-lipoxygenase pathway (required for hepA3production) could dramatically reduce PMN-mediated tissue trauma, demonstrating that hepA3is a key regulator of mucosal inflammation. |
| Databáze: | OpenAIRE |
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