A nox2/cybb zebrafish mutant with defective myeloid cell reactive oxygen species production displays normal initial neutrophil recruitment to sterile tail injuries

• Published in: G3 : genes - genomes - genetics Vol. 14; no. 6
• Main Authors: Isiaku, Abdulsalam I, Zhang, Zuobing, Pazhakh, Vahid, Lieschke, Graham J
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 02-05-2024
• Subjects: Animals; Disease Models, Animal; Genetic Models of Rare Diseases; Granulomatous Disease, Chronic - genetics; Mutation; Myeloid Cells - metabolism; NADPH Oxidase 2 - genetics; NADPH Oxidase 2 - metabolism; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; Neutrophil Infiltration; Neutrophils - metabolism; Reactive Oxygen Species - metabolism; Tail; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; acute inflammation; wound; chronic granulomatous disease; ROS; cybb; nox2; zebrafish; neutrophils; chemotaxis
• ISSN: 2160-1836; 2160-1836
• DOI: 10.1093/g3journal/jkae079

Reactive oxygen species are important effectors and modifiers of the acute inflammatory response, recruiting phagocytes including neutrophils to sites of tissue injury. In turn, phagocytes such as neutrophils are both consumers and producers of reactive oxygen species. Phagocytes including neutrophils generate reactive oxygen species in an oxidative burst through the activity of a multimeric phagocytic nicotinamide adenine dinucleotide phosphate oxidase complex. Mutations in the NOX2/CYBB (previously gp91phox) nicotinamide adenine dinucleotide phosphate 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 a nox2/cybb zebrafish (Danio rerio) mutant and demonstrated it to have severely impaired myeloid cell reactive oxygen species production. Reduced early survival of nox2 mutant embryos indicated an essential requirement for nox2 during early development. In nox2/cybb zebrafish 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. This nox2 zebrafish mutant adds to existing in vivo models for studying reactive oxygen species function in myeloid cells including neutrophils in development and disease.