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Bone marrow-derived cells require a functional glucose 6-phosphate transporter for normal myeloid functions
So Youn Kim1, Andrew D Nguyen, Ji-Liang Gao
1Section on Cellular Differentiation, Heritable Disorders Branch, NICHD, Molecular Signaling Section, Laboratory of Molecular Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
The Journal of Biological Chemistry
|August 8, 2006
Summary
Glycogen storage disease type Ib (GSD-Ib) results from glucose 6-phosphate transporter (Glc-6-PT) deficiency. This study shows Glc-6-PT in bone marrow is essential for normal myeloid cell function and neutrophil activity.
Area of Science:
- Biochemistry
- Immunology
- Genetics
Background:
- Glycogen storage disease type Ib (GSD-Ib) is linked to glucose 6-phosphate transporter (Glc-6-PT) deficiency.
- Glc-6-PT is crucial for glucose homeostasis in the liver and kidney.
- Neutrophil dysfunction and neutropenia are observed in GSD-Ib patients, but the role of bone marrow Glc-6-PT is debated.
Purpose of the Study:
- To investigate the role of Glc-6-PT in bone marrow and myeloid cell function.
- To determine if Glc-6-PT deficiency in bone marrow causes the observed myeloid abnormalities in GSD-Ib.
Main Methods:
- Generated bone marrow chimeric mice by transferring Glc-6-PT-deficient (Glc-6-PT(-/-)) or wild-type bone marrow into wild-type recipients.
- Assessed myeloid functions, including neutrophil respiratory burst, chemotaxis, and calcium flux.
- Analyzed bone marrow progenitor cell counts and serum chemokine levels in response to inflammation.
Main Results:
- Chimeric mice with Glc-6-PT-deficient bone marrow (BM-Glc-6-PT(-/-)) exhibited neutropenia and impaired neutrophil functions, similar to Glc-6-PT(-/-) mice.
- Increased myeloid progenitor cells and elevated granulocyte colony-stimulating factor and KC levels were found in the bone marrow of BM-Glc-6-PT(-/-) and Glc-6-PT(-/-) mice.
- Reduced chemokine production and neutrophil accumulation were observed in peritoneal inflammation models, with a less severe defect in BM-Glc-6-PT(-/-) mice.
Conclusions:
- Glc-6-PT expression within bone marrow and neutrophils is essential for normal myeloid cell function.
- Non-marrow Glc-6-PT activity also contributes to certain myeloid functions.
- These findings clarify the contribution of bone marrow Glc-6-PT deficiency to GSD-Ib myeloid defects.