title: Physiologic and pathologic consequences of granulocyte colony-stimulating factor deficiency.
abstract: Published studies have extended our understanding of granulocyte colony-stimulating factor deficiency. In granulocyte colony-stimulating factor withdrawal in humans, apoptosis seems to account for the dramatic loss of neutrophils, but whether the apoptosis results from normal cellular aging processes or accelerated cell loss upon granulocyte colony-stimulating factor withdrawal is unclear. In granulocyte colony-stimulating factor(-/-) mice, the introduction of bcl-2, an antiapoptotic gene product, did not affect the number of neutrophils in the circulation. This finding suggests that apoptosis does not account for the lack of neutrophils in this setting and that the reduction in neutrophil numbers in these mice results from processes other than the loss of large numbers of granulocyte colony-stimulating factor-dependent cells after commitment to the neutrophil lineage. In an experimental model of the induction of antigranulocyte colony-stimulating factor antibodies, the animals appeared remarkably similar to granulocyte colony-stimulating factor(-/-) mice. This finding confirms that at least some neutrophils are produced by granulocyte colony-stimulating factor-independent mechanisms and suggests that the antigranulocyte colony-stimulating factor antibodies reported in clinical studies before and after granulocyte colony-stimulating factor administration do not lead to similar consequences. A gross loss of neutrophils as seen in these granulocyte colony-stimulating factor-immune mice has never been reported in patients, suggesting that such an occurrence is unlikely to have occurred.
authors.affiliation: Amgen Inc., Thousand Oaks, California 91320, USA. grahamm@amgen.com
authors.forename: Graham
authors.initials: G
authors.lastname: Molineux
mesh_terms: D000818:Animals; D017209:Apoptosis; D016179:Granulocyte Colony-Stimulating Factor / Q000172:deficiency*; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor