G-CSF: a key regulator of neutrophil production, but that's not all!

Abstract

G-CSF is a major extracellular regulator of haemopoiesis and the innate immune system. Named for its relatively specific stimulation of the growth of neutrophil progenitor cells in vitro in semi-solid cultures (Burgess and Metcalf 1980, Nicola et al. 1983), G-CSF influences the survival, proliferation and differentiation of all cells in the neutrophil lineage, from haemopoietic stem cell through to mature neutrophil. Further, G-CSF influences the function of mature neutrophils. These actions underpin its rapid uptake into clinical medicine as a drug that increases the production of neutrophils in patients with chemotherapy-induced neutropenia. Ongoing research has uncovered initially unsuspected polyfunctionality for G-CSF. G-CSF is well recognised as a potent mobiliser of haemopoietic stem cells from the bone marrow into the blood, and now is being increasingly accepted as a regulator of immune responses. These two "new" actions of G-CSF first came to light through observations made during clinical trials of G-CSF. Subsequent investigations into the cellular and molecular basis for this polyfunctionality have generated exciting new knowledge about the biology of G-CSF. This review emphasises recent advances in knowledge about G-CSF signalling, mechanisms of G-CSF-induced stem cell mobilisation, and how G-CSF influences T-cell function and dendritic cell activation. An attempt is made to link the current issues about the biology of G-CSF with its clinical uses, both present and future.