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Hypochlorous acid (HOCl) regulates neutrophil extracellular trap (NET) release
Author(s) -
Palmer Lisa Joanne,
Ling Martin R,
Wright Helen J,
Cooper Paul R,
Chapple Iain L C
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.116.7
Subject(s) - myeloperoxidase , neutrophil extracellular traps , hypochlorous acid , chemistry , nadph oxidase , biochemistry , taurine , extracellular , reactive oxygen species , superoxide dismutase , superoxide , respiratory burst , antioxidant , enzyme , inflammation , biology , immunology , amino acid
Neutrophil extracellular traps (NETs) are webs of a DNA‐antimicrobial peptide complex extruded during a novel process of programmed cell death, and which kill pathogens extracellularly. The process relies upon H 2 O 2 generated by the NADPH‐oxidase and subsequent myeloperoxidase (MPO) involvement has recently been suggested. Here, we further characterise ROS regulation of NET release. Human neutrophils were incubated for 3 hours and the NETs released were then liberated into the supernatant by micrococcal nuclease digestion. NET DNA was quantified fluorometrically. MPO inhibition using 4‐aminobenzoic acid hydrazide, decreased NET release (P=0.01). Increased NET release was observed upon generation of the MPO substrate H 2 O 2 by exogenous addition of superoxide dismutase (P=0.003). Moreover, treatment of neutrophils with the MPO product, HOCl, alone was sufficient to elicit NET release (P=0.001), and removal of HOCl by pre‐incubation with taurine abolished NET release. In conclusion, this data supports a role for MPO and identifies for the first time, HOCl as the key MPO‐generated molecule required for NET release. In addition, this data provides one potential explanation for the high (millimolar) levels of cytosolic taurine present within neutrophils, as this endogenous antioxidant appears to be capable of rescuing neutrophils from a pathway of programmed cell death . Funded by University of Birmingham.