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

Publisher: Oxford University Press Country of Publication: England NLM ID: 101566598 Publication Model: Print Cited Medium: Internet ISSN: 2160-1836 (Electronic) Linking ISSN: 21601836 NLM ISO Abbreviation: G3 (Bethesda) Subsets: MEDLINE

Publication: 2021- : [Oxford] : Oxford University Press
Original Publication: Bethesda, MD : Genetics Society of America, 2011-

Zebrafish* ; Reactive Oxygen Species*/metabolism ; NADPH Oxidase 2*/genetics ; NADPH Oxidase 2*/metabolism ; Myeloid Cells*/metabolism ; Mutation*; Animals ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism ; Neutrophils/metabolism ; Neutrophil Infiltration ; Tail ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; Granulomatous Disease, Chronic/genetics ; Disease Models, Animal

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.
Competing Interests: Conflicts of interest The authors declare no conflicts of interest.
(© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

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Monash University; Graduate Scholarship and International Tuition Scholarship; 201608140011 China Scholarship Council; Maddie Riewoldt's; ARMI-MRV-2018G Vision; 1044754 National Health and Medical Research Council; DP170102235 Australian Research Council; State Government of Victoria; Australian Government

Keywords: cybb; nox2; ROS; acute inflammation; chemotaxis; chronic granulomatous disease; neutrophils; wound; zebrafish

0 (Reactive Oxygen Species)
EC 1.6.3.- (NADPH Oxidase 2)
0 (Zebrafish Proteins)
EC 1.6.3.- (NADPH Oxidases)

Date Created: 20240502 Date Completed: 20240605 Latest Revision: 20241010

20241010

PMC11152067

10.1093/g3journal/jkae079

38696730