title: Secretion of neutrophil secondary granules occurs during granulocyte-macrophage colony stimulating factor induced margination.
abstract: The effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil lactoferrin (LF) and transcobalamin (TC) 1 and 3 secretion were determined in vitro and during in vivo administration in humans. In whole blood, in vitro incubation with GM-CSF reproducibly produced a rise in plasma LF concentration (P less than 0.05) whereas in purified neutrophils the results were variable. Exposure of whole blood to GM-CSF also resulted in a significant rise in plasma TC 1 and 3 (190 +/- 60%, P less than 0.05). The response was dose dependent with maximal effect at GM-CSF concentrations of 10 ng/ml and above. rhGM-CSF was administered on seven occasions to six patients with malignant disease prior to chemotherapy. Plasma LF and unsaturated TC 1 and 3 levels rose significantly in each patient studied and the rise coincided with the initial neutropenia due to margination that occurs during infusions of rhGM-CSF. Patients receiving rhGM-CSF may therefore have hypofunctional neutrophils due to secondary granule depletion.
authors.affiliation: Department of Haematology, University College and Middlesex Hospital School of Medicine, London.
authors.forename: S
authors.initials: S
authors.lastname: Devereux
authors.forename: J B
authors.initials: JB
authors.lastname: Porter
authors.forename: K P
authors.initials: KP
authors.lastname: Hoyes
authors.forename: R D
authors.initials: RD
authors.lastname: Abeysinghe
authors.forename: R
authors.initials: R
authors.lastname: Saib
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007781:Lactoferrin / Q000097:blood; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D014155:Transcobalamins / Q000032:analysis
chemical_list: D003115:Colony-Stimulating Factors; D006133:Growth Substances; D014155:Transcobalamins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007781:Lactoferrin