The influence in vivo of murine colony-stimulating factor-1 on myeloid
progenitor cells in mice recovering from sublethal dosages of
cyclophosphamide
HE Broxmeyer, DE Williams, S Cooper, A Waheed and RK Shadduck
Pure murine colony-stimulating factor-1 (CSF-1) was assessed for its
effects in vivo in mice pretreated seven days earlier with a sublethal
dosage of cyclophosphamide. The multipotential (CFU-GEMM), erythroid
(BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in these mice
were in a slowly cycling or noncycling state. Intravenous administration of
20,000 units of CSF-1 to these mice stimulated the hematopoietic
progenitors into a rapidly cycling state in the marrow and spleen within
three hours. Significant increases in absolute numbers of marrow and spleen
CFU-GM and spleen BFU-E and CFU-GEMM were also detected. No endotoxin was
detected in the CSF-1 preparation by Limulus lysate assay, and treatment of
CSF-1 at 100 degrees C for 20 to 30 minutes completely inactivated the in
vitro and in vivo stimulating effects. The effects of CSF-1 were not
mimicked by the in vivo administration of 0.1 to 10 ng Escherichia coli
lipopolysaccharide. These results suggest that the effects of CSF-1 in vivo
were not due to contaminating endotoxin or to a nonspecific protein effect.
CSF-1 did not enhance colony formation by BFU-E or stimulate colony
formation by CFU-GEMM in vitro, thus suggesting that at least some of the
effects of CSF-1 noted in vivo are probably indirect and mediated by
accessory cells.
Volume 69,
Issue 3,
pp. 913-918,
03/01/1987
Copyright © 1987 by The American Society of Hematology