Granulocyte colony‐stimulating factor (G‐CSF) downregulates its receptor (CD114) on neutrophils and induces gelatinase B release in humans

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.