Abstract
Neutrophils from patients suffering from glycogen storage disease type Ib (GSD-Ib) show several defects, one of which is a decreased rate of glucose utilization. In this study, we established experimental conditions to show the stimulation of the neutrophil respiratory burst by extracellular glucose. With phorbol-myristate-acetate as stimulus of the burst, the activity of the NADPH oxidase in GSD-Ib neutrophils hardly increased on addition of glucose. In control and GSD-type Ia neutrophils, a clear increase was observed. The lack of response to extracellular glucose in GSD-Ib neutrophils is correlated with the inability to raise intracellular glucose-6-P levels on glucose addition, thereby limiting the activity of the generation of NADPH in the hexose-monophosphate shunt. Our study shows the usefulness of this test for the diagnosis of neutrophil function abnormality in GSD-Ib patients.
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Abbreviations
- GSD-Ia:
-
glycogen storage disease type Ia
- GSD-Ib:
-
glycogen storage disease type Ib
- G-CSF:
-
granulocyte colony-stimulating factor
- G6P:
-
glucose-6-phosphate
- HEPES:
-
hydroxy-ethyl-piperazine-ethane-sulfonic acid
- PMA:
-
phorbol-myristate-acetate
- DMSO:
-
dimethylsulfoxide
- MOPS:
-
morpholino-propane-sulfonic acid
- STZ:
-
serum-treated zymosan
- fMLP:
-
formyl-methionyl-leucyl-phenylalanine
- SOD:
-
superoxide dismutase
- PBS:
-
phosphate-buffered saline
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Acknowledgements
The authors thank Dr. A. T. J. Tool and Prof. D. Roos for their help and stimulating discussions in the course of these studies.
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Verhoeven, A., Visser, G., Van Zwieten, R. et al. A Convenient Diagnostic Function Test of Peripheral Blood Neutrophils in Glycogen Storage Disease Type Ib. Pediatr Res 45, 881–885 (1999). https://doi.org/10.1203/00006450-199906000-00018
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DOI: https://doi.org/10.1203/00006450-199906000-00018
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