Nitric oxide and peroxynitrite trigger and enhance release of neutrophil extracellular traps.

Nitric oxide and peroxynitrite trigger and enhance release of neutrophil extracellular traps. Cell Mol Life Sci. 2019 Oct 24;: Authors: Manda-Handzlik A, Bystrzycka W, Cieloch A, Glodkowska-Mrowka E, Jankowska-Steifer E, Heropolitanska-Pliszka E, Skrobot A, Muchowicz A, Ciepiela O, Wachowska M, Demkow U Abstract Despite great interest, the mechanism of neutrophil extracellular traps (NETs) release is not fully understood and some aspects of this process, e.g. the role of reactive nitrogen species (RNS), still remain unclear. Therefore, our aim was to investigate the mechanisms underlying RNS-induced formation of NETs and contribution of RNS to NETs release triggered by various physiological and synthetic stimuli. The involvement of RNS in NETs formation was studied in primary human neutrophils and differentiated human promyelocytic leukemia cells (HL-60 cells). RNS (peroxynitrite and nitric oxide) efficiently induced NETs release and potentiated NETs-inducing properties of platelet activating factor and lipopolysaccharide. RNS-induced NETs formation was independent of autophagy and histone citrullination, but dependent on the activity of phosphoinositide 3-kinases (PI3K) and myeloperoxidase, as well as selective degradation of histones H2A and H2B by neutrophil elastase. Additionally, NADPH oxidase activity was required to release NETs upon stimulation with NO, as shown in NADPH-deficient neutrophils isolated from patients with chron...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research