Lytic NET formation can be observed in neutrophils undergoing cell death, which is referred to as NETosis. Indeed, the characteristic nuclear lobules of neutrophils disappear, and neutrophils release NET-like structures of decondensed chromatin strands (called neutrophil extracellular traps, NETs) decorated with antimicrobial peptides, for trapping and possibly killing microorganisms. Neutrophil granulocytes are polymorphonuclear cells that migrate to sites of infection (as part of the first line of immune defense) where they phagocytose, degranulate and/or, in the presence of appropriate stimuli, they may undergo marked morphological cell changes, in particular within the nucleus. The identification of novel vanilloid NET inhibitors, able to stop excessive or aberrant NET production might offer new therapeutic options for those disorders displaying NET overproduction. Vanilloids also markedly decrease cytosolic ROS production. By employing a phenotypic assay based on high-content imaging and analysis, we screened a library of biologically active compounds and identified vanilloids as a novel class of chemical compounds able to hinder NETosis induction and NET release. Dysregulation of NET production and/or degradation can exert pathogenic effects, contributing to the pathogenesis of various diseases, including cystic fibrosis, autoimmune diseases and inflammatory conditions. NET formation is characterized by marked morphological cell changes, in particular within the nucleus. Neutrophils migrate to sites of infection where they phagocytose, degranulate, and/or, in the presence of appropriate stimuli, release decondensed chromatin strands (called neutrophil extracellular traps, NETs) for trapping and possibly killing microorganisms.
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