A Lipid Mediator Hepoxilin A3 Is a Natural Inducer of Neutrophil Extracellular Traps in Human Neutrophils
| Autor: | Hartmut Grasemann, Nades Palaniyar, Cecil R. Pace-Asciak, David N. Douda |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Article Subject
Cystic Fibrosis Neutrophils Immunology Inflammation Biology Cystic fibrosis Extracellular Traps Proinflammatory cytokine chemistry.chemical_compound 8 11 14-Eicosatrienoic Acid medicine lcsh:Pathology Humans Cells Cultured Lung Cell Biology Neutrophil extracellular traps respiratory system medicine.disease Neutrophilia 3. Good health respiratory tract diseases medicine.anatomical_structure chemistry Eicosanoid Hepoxilin medicine.symptom Research Article lcsh:RB1-214 |
| Zdroj: | Mediators of Inflammation, Vol 2015 (2015) Mediators of Inflammation |
| ISSN: | 1466-1861 0962-9351 |
| Popis: | Pulmonary exacerbations in cystic fibrosis airways are accompanied by inflammation, neutrophilia, and mucous thickening. Cystic fibrosis sputum contains a large amount of uncleared DNA contributed by neutrophil extracellular trap (NET) formation from neutrophils. The exact mechanisms of the induction of NETosis in cystic fibrosis airways remain unclear, especially in uninfected lungs of patients with early cystic fibrosis lung disease. Here we show that Hepoxilin A3, a proinflammatory eicosanoid, and the synthetic analog of Hepoxilin B3, PBT-3, directly induce NETosis in human neutrophils. Furthermore, we show that Hepoxilin A3-mediated NETosis is NADPH-oxidase-dependent at lower doses of Hepoxilin A3, while it is NADPH-oxidase-independent at higher doses. Together, these results demonstrate that Hepoxilin A3 is a previously unrecognized inducer of NETosis in cystic fibrosis lungs and may represent a new therapeutic target for treating cystic fibrosis and other inflammatory lung diseases. |
| Databáze: | OpenAIRE |
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