Please use this identifier to cite or link to this item: https://doi.org/10.1172/JCI91684
Title: NBEAL2 is required for neutrophil and NK cell function and pathogen defense
Authors: Sowerby, J.M
Thomas, D.C
Clare, S
Espéli, M
Guerrero, J.A
Hoenderdos, K
Harcourt, K
Marsden, M
Abdul-Karim, J
Clement, M
Antrobus, R
Umrania, Y
Barton, P.R
Flint, S.M
Juss, J.K
Condliffe, A.M
Lyons, P.A
Humphreys, I.R
Chilvers, E.R
Ouwehand, W.H
Dougan, G
Smith, K.G.C 
Keywords: reduced nicotinamide adenine dinucleotide phosphate oxidase
superoxide
NBEAL2 protein, human
plasma protein
reduced nicotinamide adenine dinucleotide phosphate oxidase
animal cell
animal experiment
animal model
Article
cell function
Cytomegalovirus
cytomegalovirus infection
degranulation
gene
immune system
immunity
mouse
natural killer cell
nbeal2 gene
neutrophil
nonhuman
phagocyte
phenotype
priority journal
respiratory burst
Staphylococcus aureus
animal
cytosol
genetics
gray platelet syndrome
human
immunophenotyping
knockout mouse
metabolism
mutation
natural killer cell
neutrophil
Staphylococcus infection
thrombocyte
Animals
Blood Platelets
Blood Proteins
Cytosol
Gray Platelet Syndrome
Humans
Immune System
Immunophenotyping
Killer Cells, Natural
Mice
Mice, Knockout
Mutation
NADPH Oxidase
Neutrophils
Phenotype
Staphylococcal Infections
Staphylococcus aureus
Issue Date: 2017
Publisher: American Society for Clinical Investigation
Citation: Sowerby, J.M, Thomas, D.C, Clare, S, Espéli, M, Guerrero, J.A, Hoenderdos, K, Harcourt, K, Marsden, M, Abdul-Karim, J, Clement, M, Antrobus, R, Umrania, Y, Barton, P.R, Flint, S.M, Juss, J.K, Condliffe, A.M, Lyons, P.A, Humphreys, I.R, Chilvers, E.R, Ouwehand, W.H, Dougan, G, Smith, K.G.C (2017). NBEAL2 is required for neutrophil and NK cell function and pathogen defense. Journal of Clinical Investigation 127 (9) : 3521-3526. ScholarBank@NUS Repository. https://doi.org/10.1172/JCI91684
Rights: Attribution 4.0 International
Abstract: Mutations in the human NBEAL2 gene cause gray platelet syndrome (GPS), a bleeding diathesis characterized by a lack of ? granules in platelets. The functions of the NBEAL2 protein have not been explored outside platelet biology, but there are reports of increased frequency of infection and abnormal neutrophil morphology in patients with GPS. We therefore investigated the role of NBEAL2 in immunity by analyzing the phenotype of Nbeal2-deficient mice. We found profound abnormalities in the Nbeal2-deficient immune system, particularly in the function of neutrophils and NK cells. Phenotyping of Nbeal2-deficient neutrophils showed a severe reduction in granule contents across all granule subsets. Despite this, Nbeal2-deficient neutrophils had an enhanced phagocyte respiratory burst relative to Nbeal2-expressing neutrophils. This respiratory burst was associated with increased expression of cytosolic components of the NADPH oxidase complex. Nbeal2- deficient NK cells were also dysfunctional and showed reduced degranulation. These abnormalities were associated with increased susceptibility to both bacterial (Staphylococcus aureus) and viral (murine CMV) infection in vivo. These results define an essential role for NBEAL2 in mammalian immunity.
Source Title: Journal of Clinical Investigation
URI: https://scholarbank.nus.edu.sg/handle/10635/179095
ISSN: 00219738
DOI: 10.1172/JCI91684
Rights: Attribution 4.0 International
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