In vivo stimulation of myelopoiesis in cyclophosphamide-treated mice by purified human GM-CSF.
Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) secreted by a hepatoma cell line, HA22T/GVH, was purified and assessed for its effects in vivo on blood leukocytes and bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in ICR mice pretreated with a sublethal dose of cyclophosphamide (cytoxan). The hGM-CSF preparations were natural and had no detectable endotoxin. Five days after the administration of 300 mg/kg cytoxan, severe leukopenia with marked myelopoietic suppression was induced. The cytoxan-treated mice were then injected intraperitoneally with 10,000 units of purified hGM-CSF/mouse daily for three days. Leukopenia was totally abrogated and the leukocyte number greatly increased to a level 2- to 3-fold higher than in GM-CSF-uninjected mice. Differential white cell count showed that the subpopulations of leukocytes responsive to hGM-CSF stimulation were mainly of neutrophils and monocytes, while the lymphocytes remained unaffected. Meanwhile, in the bone marrow, hGM-CSF administration induced an apparent (3-fold) increase in the number of myeloid progenitor cells, CFU-GM. However, the effect in vivo of a single hGM-CSF injection could only maintain for 48 hrs. In addition, the loss in body weight caused by cytoxan was less in the mice with subsequent hGM-CSF than those without CSF. These results suggest that injection of GM-CSF can effectively reconstitute the cytotoxic drug-damaged myelopoiesis without apparent in vivo toxic reaction.
Wang
S Y
SY
Department of Medical Research, Veterans General Hospital-Taipei, National Yang-Ming Medical College, R.O.C.
Hsu
M L
ML
Su
C Y
CY
Lin
C K
CK
Hu
C P
CP
Chang
C M
CM
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D003520:Cyclophosphamide / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide