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

• DOI: 10.1007/s00018-019-03331-x
• Publication Date: 2019-10-25T03:58:13Z
• Authors: Aneta Manda-Handzlik; Weronika Bystrzycka; Adrianna Cieloch; Eliza Glodkowska-...; Ewa Jankowska-Ste...; Edyta Heropolitan...; Agnieszka Skrobot; Angelika Muchowicz; Olga Ciepiela; Malgorzata Wachowska; Urszula Demkow
• Keywords: Neutrophil Extracellular Traps; Peroxynitrous acid

Despite great interest, the mechanism of neutrophil extracellular traps (NETs) release is not fully understood and some aspects this process, e.g. role reactive nitrogen species (RNS), still remain unclear. Therefore, our aim was to investigate mechanisms underlying RNS-induced formation NETs contribution RNS triggered by various physiological synthetic stimuli. The involvement in studied primary human neutrophils differentiated promyelocytic leukemia cells (HL-60 cells). (peroxynitrite nitric oxide) efficiently induced potentiated NETs-inducing properties platelet activating factor lipopolysaccharide. independent autophagy histone citrullination, but dependent on activity phosphoinositide 3-kinases (PI3K) myeloperoxidase, as well selective degradation histones H2A H2B elastase. Additionally, NADPH oxidase required upon stimulation with NO, shown NADPH-deficient isolated from patients chronic granulomatous disease. further supported increased synthesis phorbol 12-myristate 13-acetate calcium ionophore A23187. Scavenging or inhibition diminished these stimuli while scavenging peroxynitrite inhibited NO-induced formation. Our data suggest that may act mediators inducers release. These processes are PI3K-dependent ROS-dependent. Since inflammatory reactions often accompanied nitrosative stress formation, studies shed a new light possible engaged immune-mediated conditions.