Anox2/cybbzebrafish mutant with defective neutrophil ROS production displays normal initial neutrophil recruitment to sterile tail injuries

Abstract

AbstractReactive oxygen species (ROS) are important effectors and modifiers of the acute inflammatory response, recruiting neutrophils to sites of tissue injury. In turn, neutrophils are both consumers and producers of reactive oxygen species. Stimulated neutrophils generate reactive oxygen species in an oxidative burst through the activity of a multimeric phagocytic NADPH oxidase complex. Mutations in theNOX2/CYBB(previously gp91phox) NADPH oxidase subunit are the commonest cause of chronic granulomatous disease, a disease characterized by infection susceptibility and an inflammatory phenotype. To model chronic granulomatous disease, we made anox2/cybbzebrafish (Danio rerio) mutant and demonstrated it to have severely impaired neutrophil ROS production. Reduced early survival ofnox2mutant embryos indicated an essential requirement fornox2during early development. Innox2/cybbzebrafish mutants, the dynamics of initial neutrophil recruitment to both mild and severe surgical tailfin wounds was normal, suggesting that excessive neutrophil recruitment at the initiation of inflammation is not the primary cause of the “sterile” inflammatory phenotype of chronic granulomatous disease patients. Thisnox2zebrafish mutant adds to existing in vivo models for studying neutrophil reactive oxygen species function in development and disease.