A lipid mediator hepoxilin A3 is a natural inducer of neutrophil extracellular traps in human neutrophils

Mediators of Inflammation
David N DoudaNades Palaniyar

Abstract

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.

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Citations

Apr 20, 2016·Nature Communications·Gajanan D KatkarKempaiah Kemparaju
Aug 31, 2016·Frontiers in Immunology·Bárbara Nery Porto, Renato Tetelbom Stein
Nov 5, 2016·Scientific Reports·Manjunath B JoshiKapaettu Satyamoorthy
Feb 9, 2017·Scientific Reports·Meraj A Khan, Nades Palaniyar
Nov 11, 2017·Frontiers in Immunology·Ljubomir VitkovMatthias Hannig
Jan 11, 2021·Clinical Pharmacology and Therapeutics·Lael M YonkerBryan P Hurley
Oct 9, 2020·The Journal of Pain : Official Journal of the American Pain Society·Anthony F DomenichielloChristopher E Ramsden
Jan 30, 2018·ACS Chemical Biology·Laura R ParisiG Ekin Atilla-Gokcumen

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Methods Mentioned

BETA
blood collection

Software Mentioned

Volocity
GraphPad Prism

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