Mature and immature myeloid cells decrease the granulocyte colony-stimulating factor level by absorption of granulocyte colony-stimulating factor.
We studied the effects of polymorphonuclear neutrophils (PMN) and immature myeloid cells on the granulocyte colony-stimulating factor (G-CSF) level in vitro to better understand the regulatory mechanisms of neutropoiesis. Intact normal PMN decreased the G-CSF level after incubation with recombinant human (rh) G-CSF in a time- and dose-dependent manner. The percent reduction decreased as the concentration of rhG-CSF increased. However, the cell-free PMN-conditioned medium (PMN-CM) did not decrease the G-CSF level. The intact PMN also decreased the granulocyte-macrophage (GM)-CSF level after culture with rhGM-CSF, but did not affect the monocyte (M)-CSF level after culture with rhM-CSF. Normal bone marrow (BM) immature neutrophilic cells and G-CSF-dependent acute myeloid leukemic cells (OCI/AML la) also decreased the G-CSF level, whereas K-562 cells, which have no detectable G-CSF receptors, did not affect it. Phenylarsine oxide (PhAsO), an inhibitor of endocytosis of ligand receptor complex, abrogated this decreasing effect of intact PMN and OCI/AML la cells. These findings suggest that mature and immature myeloid cells negatively regulate neutropoiesis by, at least in part, decreasing the G-CSF level probably through receptor-mediated continual absorption and metabolism of G-CSF.
Saito
K
K
Third Department of Internal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Nakamura
Y
Y
Waga
K
K
Hirota
K
K
Inoue
F
F
Enokihara
H
H
Nara
N
N
Furusawa
S
S
D000042:Absorption; D000367:Age Factors; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002448:Cell Adhesion; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000493:pharmacokinetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000493:pharmacokinetics; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000493:pharmacokinetics; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013601:T-Lymphocytes / Q000166:cytology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor