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Granulocyte colony-stimulating factor (G-CSF) downregulates its receptor (CD114) on neutrophils and induces gelatinase B release in humans.
- Source :
-
British Journal of Haematology . Oct2000, Vol. 111 Issue 1, p314-320. 7p. 1 Diagram, 3 Graphs. - Publication Year :
- 2000
-
Abstract
- Despite the increasing use of granulocyte colony-stimulating factor (G-CSF) for the mobilization of stem cells and neutrophils, its pharmacodynamic actions are not fully understood. Because of the roles of G-CSF and gelatinase B in leucokinetics, we set out to characterize the interaction of G-CSF with its receptor in humans and its effects on gelatinase B release. G-CSF was infused at bolus doses of 1 μg/kg and 5 μg/kg, and compared to placebo and dexamethasone (1 mg/kg b.i.d), which enhances the plasma levels of endogenous G-CSF. The study was randomized, double-blind, four-way crossover, in eight healthy male volunteers. G-CSF dose-independently induced profound neutropenia (> 95%) within minutes and downregulated its own receptor (CD114) on neutrophils by 75%. The G-CSF/CD114 interaction dose-independently induced degranulation of neutrophils as evidenced by a 300–400% increase in CD11b expression. Degranulation induced up to a 10-fold increase in plasma levels of gelatinase B, an enzyme known to precipitate neutropenia and subsequent neutrophilia in animals. In this study, it was shown that G-CSF downmodulates CD114 expression on the surface of neutrophils in humans and the consequent degranulation enhances gelatinase B release into plasma, which may contribute to mobilization of neutrophils or stem cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00071048
- Volume :
- 111
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- British Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 5605041
- Full Text :
- https://doi.org/10.1046/j.1365-2141.2000.02320.x