Abstract
Neutrophils (PMNs) and cytokines have a critical role to play in host defense and systemic inflammatory response syndrome (SIRS). Neutrophil extracellular traps (NETs) have been shown to extracellularly kill pathogens, and inflammatory potential of NETs has been shown. Microbial killing inside the phagosomes or by NETs is mediated by reactive oxygen and nitrogen species (ROS/RNS). The present study was undertaken to assess circulating NETs contents and frequency of NETs generation by isolated PMNs from SIRS patients. These patients displayed significant augmentation in the circulating myeloperoxidase (MPO) activity and DNA content, while PMA stimulated PMNs from these patients, generated more free radicals and NETs. Plasma obtained from SIRS patients, if added to the PMNs isolated from healthy subjects, enhanced NETs release and free radical formation. Expressions of inflammatory cytokines (IL-1β, TNFα and IL-8) in the PMNs as well as their circulating levels were significantly augmented in SIRS subjects. Treatment of neutrophils from healthy subjects with TNFα, IL-1β, or IL-8 enhanced free radicals generation and NETs formation, which was mediated through the activation of NADPH oxidase and MPO. Pre-incubation of plasma from SIRS with TNFα, IL-1β, or IL-8 antibodies reduced the NETs release. Role of IL-1β, TNFα and IL-8 thus seems to be involved in the enhanced release of NETs in SIRS subjects.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Adult
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Aged
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Cells, Cultured
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Cytokines / genetics
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Cytokines / immunology*
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Cytokines / pharmacology
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DNA / blood
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DNA / immunology
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DNA / metabolism
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Electron Transport Complex IV / genetics
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Female
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Humans
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Inflammation Mediators / blood
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Inflammation Mediators / immunology*
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Inflammation Mediators / metabolism
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Interleukin-1beta / genetics
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Interleukin-1beta / immunology
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Interleukin-1beta / pharmacology
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Interleukin-8 / genetics
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Interleukin-8 / immunology
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Interleukin-8 / pharmacology
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Male
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Middle Aged
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Mitochondrial Proton-Translocating ATPases / genetics
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Neutrophil Activation / drug effects
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Neutrophil Activation / immunology
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Neutrophils / drug effects
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Neutrophils / immunology*
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Neutrophils / metabolism
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Peroxidase / blood
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Peroxidase / immunology
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Peroxidase / metabolism
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Reactive Oxygen Species / immunology
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Reactive Oxygen Species / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Systemic Inflammatory Response Syndrome / blood
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Systemic Inflammatory Response Syndrome / immunology*
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / pharmacology
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Young Adult
Substances
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Actins
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Cytokines
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Inflammation Mediators
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Interleukin-1beta
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Interleukin-8
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MT-ATP6 protein, human
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Reactive Oxygen Species
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Tumor Necrosis Factor-alpha
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DNA
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Peroxidase
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Electron Transport Complex IV
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Mitochondrial Proton-Translocating ATPases
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Tetradecanoylphorbol Acetate
Grants and funding
The study was supported by a financial grant to Madhu Dikshit from the Department of Biotechnology-INDIGO project (BT/IN/New Indigo/08/MD/2010). Award of research fellowships to RSK, AJ and MD from the Council of Scientific and Industrial Research, India is acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.