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Neutrophil extracellular trap formation by nitric oxide donors: Involvement of nitric oxide synthase and myeloperoxidase derived free radicals
Author(s) -
Patel Satyananda,
Kumar Sachin,
Saluja Rohit,
Barthwal Manoj Kumar,
Mitra Kalyan,
Verma Anupam,
Bajpai Virendra K,
Dikshit Madhu
Publication year - 2008
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.22.1_supplement.1072.9
Subject(s) - myeloperoxidase , chemistry , nitric oxide synthase , neutrophil extracellular traps , nitric oxide , nadph oxidase , biochemistry , apocynin , inflammation , extracellular , mapk/erk pathway , sodium nitroprusside , pharmacology , kinase , enzyme , immunology , biology , organic chemistry
Presence of neutrophil extracellular traps (NET) at the site of inflammation and infection is demonstrated in various pathological conditions. Neutrophils migration and augmentation in NO availability are mostly associated with inflammation and pathogen infections. So far role of NO has not been explored in NET formation. Present study reports for the first time that incubation of human neutrophils with NO donors, sodium nitroprusside (SNP) or S ‐nitroso‐ N ‐acetyl‐penicillamine (SNAP) led to the NET release and free radical generation, which was blocked in the presence of free radical scavengers (ebselen, NAC) or pretreatment of PMNs with inhibitors of NOS reductase domain (7‐NI, DPI, imidazole) and myeloperoxidase (ABAH), while NOS oxygenase domain inhibitors had no effect. We thus propose that NO mediated NET release was dependent on the NO synthase (NOS) uncoupling and MPO derived free radicals, but independent of NADPH‐oxidase. Moreover, NO dependent free radical generation, NET release and phosphorylation of MEK/ERK, p38MAPK was blocked by inhibitors of MEK/ERK (U0126), p38MAPK (SB202190), PKC (Rottlerin) suggesting for the first time role of ERK and p38MAPK in NET formation. The results of the present study seem to have important bearing on the role of NO in inflammatory pathological conditions. The work was supported by CSIR and DBT India