title: Hypochlorous acid regulates neutrophil extracellular trap release in humans.
abstract: Neutrophil extracellular traps (NETs) comprise extracellular chromatin and granule protein complexes that immobilize and kill bacteria. NET release represents a recently discovered, novel anti-microbial strategy regulated non-exclusively by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generation of reactive oxygen intermediates (ROIs), particularly hydrogen peroxide. This study aimed to characterize the role of ROIs in the process of NET release and to identify the dominant ROI trigger. We employed various enzymes, inhibitors and ROIs to record their effect fluorometrically on in vitro NET release by human peripheral blood neutrophils. Treatment with exogenous superoxide dismutase (SOD) supported the established link between hydrogen peroxide and NET production. However, treatment with myeloperoxidase inhibitors and direct addition of hypochlorous acid (HOCl; generated in situ from sodium hypochlorite) established that HOCl was a necessary and sufficient ROI for NET release. This was confirmed by the ability of HOCl to stimulate NET release in chronic granulomatous disease (CGD) patient neutrophils which, due to the lack of a functional NADPH oxidase, also lack the capacity for NET release in response to classical stimuli. Moreover, the exogenous addition of taurine, abundantly present within the neutrophil cytosol, abrogated NET production stimulated by phorbol myristate acetate (PMA) and HOCl, providing a novel mode of cytoprotection by taurine against oxidative stress by taurine.
authors.affiliation: Periodontal Research Group and MRC Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Palmer
authors.forename: P R
authors.initials: PR
authors.lastname: Cooper
authors.forename: M R
authors.initials: MR
authors.lastname: Ling
authors.forename: H J
authors.initials: HJ
authors.lastname: Wright
authors.forename: A
authors.initials: A
authors.lastname: Huissoon
authors.forename: I L C
authors.initials: IL
authors.lastname: Chapple
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001770:Blood Bactericidal Activity / Q000187:drug effects* / Q000502:physiology; D002843:Chromatin / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism*; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000201:enzymology / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide; D006997:Hypochlorous Acid / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009895:Opsonin Proteins; D009195:Peroxidase / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species; D013211:Staphylococcus aureus; D013482:Superoxide Dismutase / Q000494:pharmacology; D013654:Taurine / Q000494:pharmacology / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D002843:Chromatin; D009895:Opsonin Proteins; D017382:Reactive Oxygen Species; D013654:Taurine; D003571:Cytochalasin B; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate