Department of Biochemistry and Molecular Pharmacology
Biochemistry | Cell Biology | Enzymes and Coenzymes | Immunology and Infectious Disease | Medicinal-Pharmaceutical Chemistry | Therapeutics
Neutrophils release neutrophil extracellular traps (NETs) which ensnare pathogens and have pathogenic functions in diverse diseases. We examined the NETosis pathways induced by five stimuli; PMA, the calcium ionophore A23187, nigericin, Candida albicans and Group B Streptococcus. We studied NET production in neutrophils from healthy donors with inhibitors of molecules crucial to PMA induced NETs including protein kinase C, calcium, reactive oxygen species, the enzymes myeloperoxidase (MPO) and neutrophil elastase. Additionally, neutrophils from chronic granulomatous disease patients, carrying mutations in the NADPH oxidase complex or a MPO-deficient patient were examined. We show that PMA, C. albicans and GBS use a related pathway for NET induction whereas ionophores require an alternative pathway but that NETs produced by all stimuli are proteolytically active, kill bacteria and composed mainly of chromosomal DNA. Thus, we demonstrate that NETosis occurs through several signalling mechanisms, suggesting that extrusion of NETs is important in host defence.
cell biology, human, immunology
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© 2017, Kenny et al.
DOI of Published Version
Elife. 2017 Jun 2;6. pii: e24437. doi: 10.7554/eLife.24437. [Epub ahead of print] Link to article on publisher's website
Kenny, Elaine F.; Herzig, Alf; Krüger, Renate; Muth, Aaron; Mondal, Santanu; Thompson, Paul R.; Brinkmann, Volker; Von Bernuth, Horst; and Zychlinsky, Arturo, "Diverse stimuli engage different neutrophil extracellular trap pathways" (2017). Thompson Lab Publications. 114.
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