SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx
Abstract
Formation of neutrophil extracellular traps (NETs) is a recently described process by which neutrophils combat microbial pathogens. Recent studies demonstrate causative relationships between NETs and debilitating disorders such as rheumatoid arthritis, vasculitis, thrombosis, cystic fibrosis, and acute respiratory distress syndrome. However, the understanding of signaling pathways governing the process termed "NETosis" remains elusive. Two major types of NETosis have been reported; however, the mechanistic differences between these two types are not clearly established. Here we describe that NETosis induced by calcium ionophores is fast, NADPH-oxidase independent, and is mediated by mitochondrial reactive oxygen species (ROS) and a calcium-activated small conductance potassium channel. Thus, drugs that target mitochondrial ROS production or the potassium channels may provide previously unidentified therapeutic approaches for combating disorders with unregulated NETosis.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2015
- DOI:
- 10.1073/pnas.1414055112
- Bibcode:
- 2015PNAS..112.2817D