Kinetics of human hemopoietic cells after in vivo administration of granulocyte-macrophage colony-stimulating factor

J Clin Invest. 1989 Feb;83(2):551-7. doi: 10.1172/JCI113917.

Abstract

The kinetic changes induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) on hemopoietic cells were assessed in physiological conditions by administering GM-CSF (8 micrograms/kg per d) for 3 d to nine patients with solid tumors and normal bone marrow (BM), before chemotherapy. GM-CSF increased the number of circulating granulocytes and monocytes; platelets, erythrocytes, lymphocyte number, and subsets were unmodified. GM-CSF increased the percentage of BM S phase BFU-E (from 32 +/- 7 to 79 +/- 16%), day 14 colony-forming unit granulocyte-macrophage (CFU-GM) (from 43 +/- 20 to 82 +/- 11%) and day 7 CFU-GM (from 41 +/- 14 to 56 +/- 20%). The percentage of BM myeloblasts, promyelocytes, and myelocytes in S phase increased from 26 +/- 14 to 41 +/- 6%, and that of erythroblasts increased from 25 +/- 12 to 30 +/- 12%. This suggests that GM-CSF activates both erythroid and granulomonopoietic progenitors but that, among the morphologically recognizable BM precursors, only the granulomonopoietic lineage is a direct target of the molecule. GM-CSF increased the birth rate of cycling cells from 1.3 to 3.4 cells %/h and decreased the duration of the S phase from 14.3 to 9.1 h and the cell cycle time from 86 to 26 h. After treatment discontinuation, the number of circulating granulocytes and monocytes rapidly fell. The proportion of S phase BM cells dropped to values lower than pretreatment levels, suggesting a period of relative refractoriness to cell cycle-active antineoplastic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / drug effects
  • Cell Division
  • Colony-Stimulating Factors / pharmacology*
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Growth Substances / pharmacology*
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Neoplasms / metabolism
  • Neoplasms / pathology

Substances

  • Colony-Stimulating Factors
  • Growth Substances
  • Granulocyte-Macrophage Colony-Stimulating Factor