Stable redox-cycling nitroxide Tempol inhibits NET formation

Frontiers in Immunology

Constantin Felix Urban¹  Philipp Karl Messer¹  Ava eHosseinzadeh¹ 

[1] Umeå University;

关键词: Neutrophils;    Reactive Oxygen Species;    neutrophil extracellular traps;    Nitroxide;    Tempol;    NET inhibition;   

DOI  :  10.3389/fimmu.2012.00391

来源: DOAJ

【 摘 要 】

To prevent the spread of pathogens neutrophils as the first line of defence are able to release Neu-trophil Extracellular Traps (NETs), a recently discovered form of immune response. Reactive oxygen species (ROS) have been shown to be essential for many different induction routes of NET formation. Therefore, pharmacological inhibition of ROS generation has implications for research and medicine related to NETs. The application of diphenylene iodonium (DPI), an inhibitor of NADPH oxidase activity, is limited due to its toxicity to host cells as well as microbes. Therefore, we investigated the effect of 4-Hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) a mem-brane-permeable radical scavenger on NET formation triggered by phorbol esters and C. albicans. We quantified the amount of NETs with two complementary methods, using a microscopic analysis and an online fluorescence-based assay. In line with removal of ROS, Tempol reduced the amount of NET formation by neutrophils challenged with those stimuli significantly. Since Tempol effi-ciently blocks NET formation in vitro, it might be promising to test the effect of Tempol in experi-mental models of disorders in which NETs probably have hazardous effects.

【 授权许可】

Unknown