The neurotransmitter GABA is a potent inhibitor of the stromal cell-derived factor-1alpha induced migration of adult CD133+ hematopoietic stem and progenitor cells.
Stem Cells Dev
; 16(5): 827-36, 2007 Oct.
Article
in En
| MEDLINE
| ID: mdl-17999603
ABSTRACT
The ability of hematopoietic stem and progenitor cells (HSPCs) to migrate is a prerequisite for bone marrow homing and tissue regeneration processes. Induction of HSPC migration is chiefly directed by stromal cell-derived factor-1alpha (SDF-1alpha). Considerably less is known about factors that terminate HSPC migration. Adult CD133(+) HSPCs were isolated from mobilized peripheral blood by immunomagnetic separation. Cell migration was assessed using the three-dimensional collagen matrix migration assay, which allows detailed migration analysis on a cell population and single-cell level. The SDF-1alpha-induced locomotory activity of CD133(+) cells was efficiently blocked by the neurotransmitter gamma-aminobutyric acid (GABA). GABA signaling was effected via the GABA(B)-receptor. This was verified by flow cytometry and cell migration studies using the specific GABA(A)-receptor and GABA(B)-receptor agonists isoguvacine and baclofen, respectively. Baclofen blocked SDF-1alpha-induced migration of CD133(+) cells. Flow cytometry-based calcium measurements revealed that GABA inhibits the SDF-1alpha-induced migration of CD133(+) cells by blocking the SDF-1alpha-induced calcium influx. Similar results were obtained with the specific calcium-release-activated calcium (CRAC) channel inhibitor BTP-2, which both blocked the SDF-1alpha-induced calcium influx and migration of CD133(+) cells. These results suggest that GABA(B)-receptor signaling modulates the activity of CRAC channels, whereby the mechanism in detail remains unclear. In summary, the neurotransmitter GABA is a potent blocker of the SDF-1alpha-induced migration of CD133(+) HSPCs from mobilized peripheral blood.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Hematopoietic Stem Cells
/
Glycoproteins
/
Antigens, CD
/
Cell Movement
/
Adult Stem Cells
/
Chemokine CXCL12
/
Gamma-Aminobutyric Acid
Limits:
Humans
Language:
En
Journal:
Stem Cells Dev
Journal subject:
HEMATOLOGIA
Year:
2007
Document type:
Article
Affiliation country:
Germany