The influence of recombinant human granulocyte colony-stimulating factor on granulopoiesis in mice recovering from cyclophosphamide treatment.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was evaluated for its effects on granulopoiesis recovery in mice pretreated with cyclophosphamide. The cytotoxic agent was administered on days 0 and 7. rhG-CSF therapy (injected from days 8 to 28) accelerated the recovery and maintained an increased level of peripheral blood neutrophils. Marrow granuloid precursors depression, due the second dose of cyclophosphamide, was prevented by rhG-CSF, but this hemopoietic growth factor was unable to increase these cells in a similar way to that observed in normal mice. This suggests a decreased granuloid marrow proliferation capacity in cyclophosphamide treated mice. In contrast, in the spleen, rhG-CSF highly increased granuloid precursors. However, the contribution of spleen to granuloid recovery was scarce. Mice receiving rhG-CSF after cyclophosphamide demonstrated a biphasic recovery pattern in bone marrow GM-CFU population. A first rebound of GM-CFUs was followed by a nadir and then a second recovery where GM-CFU progenitor cells were significantly increased was observed. On the other hand, rhG-CSF therapy highly increased the spleen GM-CFU numbers at days 24 to 28. Although rhG-CSF increased splenic granulopoiesis, this result shows that the bulk of granulopoiesis recovery due to rhG-CSF therapy in cyclophosphamide pretreated mice occurred in the marrow.
Barrios
L
L
Faculty of Medicine, Department of Basic Sciences, National Northeast University, Corrientes, Argentina. lbarrios@med.unne.edu.ar
Poletti
O H
OH
Agustini
M I
MI
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects; D002452:Cell Count; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006099:Granuloma / Q000139:chemically induced* / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide