Effect of N-methionine-free, bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in a primate model.
We demonstrate the in vivo effects of bacterially synthesized, N-methionine-free recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) using a crab-eating monkey model. Monkeys were treated with cyclophosphamide (60 mg/kg) and administered with rh GM-CSF (30 micrograms/kg/d) subcutaneously (s.c.) for 7 days. Within 12 h, a transient increase of neutrophils (greater than 15.0 x 10(9)/l) was observed, and complete recovery of WBC counts was obtained by d 9 (d 16 in control monkeys). Neutrophils and eosinophils were absolutely increased (greater than 8 x 10(9)/l) on d 10. Readministration of rh GM-CSF (30 micrograms/kg/d, s.c.) for 3 d (including control monkeys) revealed absolute increases of neutrophils, eosinophils, monocytes and platelets. A two-fold increase of granulocyte/macrophage colony-forming units was also seen in the bone marrow, while the number of burst-forming units-erythroid was not affected. These data indicate that rh GM-CSF of this type stimulates granulopoiesis and thrombopoiesis in vivo.
Akashi
K
K
First Department of Internal Medicine, Faculty of Medicine Kyushu University, Fukuoka, Japan.
Taniguchi
S
S
Teshima
T
T
Shibuya
T
T
Okamura
T
T
Harada
M
M
Niho
Y
Y
D000818:Animals; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D008715:Methionine; D009154:Mutation; D010976:Platelet Count / Q000187:drug effects*; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000494:pharmacology; D012016:Reference Values
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D008715:Methionine