[Pharmacokinetics of hematopoietic growth factors and granulopoiesis. The pathophysiology of human granulocyte colony-stimulating factor].
We have studied the production of human granulocyte colony-stimulating factor (hG-CSF). Enzyme immunoassay showed that hG-CSF was produced by primary bone marrow stromal cells, peripheral blood monocytes, fibroblasts, and endothelial cells in vitro. These cells produced variable levels of hG-CSF depending on the type of inducers. Interestingly, in situ hybridization showed that only a small proportion of bone marrow stromal cells and blood monocytes expressed a large amount of hG-CSF mRNA. Secondly, we have estimated serum hG-CSF level and clearance of exogenous hG-CSF in patients with various hematological disorders. Endogenous hG-CSF was undetectable (< 30 pg/ml) in sera of normal volunteers. On the other hand, the serum hG-CSF level was elevated in infection, malignancy, and neutropenia, suggesting the presence of reactive, ectopic, and unknown mechanisms for hG-CSF production, respectively. The half-life of recombinant hG-CSF was prolonged in disorders with reduced myeloid cell mass, especially in aplastic anemia, whereas it was shortened in myeloid leukemia, and in recovery phase after chemotherapy. This finding suggests the possibility of receptor-mediated consumption of hG-CSF in vivo. These in vitro and in vivo studies on hG-CSF would be of value for understanding the pathophysiological roles of hG-CSF.
Watari
K
K
Department of Hematology/Oncology, University of Tokyo.
D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006098:Granulocytes / Q000502:physiology*; D006402:Hematologic Diseases / Q000097:blood; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D011994:Recombinant Proteins / Q000378:metabolism
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor