Comparison of bone marrow progenitors responsive to granulocyte-macrophage colony stimulating factor and macrophage colony stimulating factor-1.
The responsiveness of bone marrow progenitors (BMP) from C3H mice to highly purified or recombinant preparations of Macrophage Colony-Stimulating Factor-1 (CSF-1) and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) was compared by counting the number of colonies (greater than or equal to 50 cells) after 10 days in culture with CSF. Cells responsive to CSF-1 or GM-CSF exhibited maximum colony formation over a wide dose range, although GM-CSF supported colony formation at lower concentrations. The response of BMP to optimal concentrations of CSF-1 was greater than or equal to 5 times greater than the response of BMP to GM-CSF. Analysis of the kinetics of colony formation revealed that, at day 5, the number of BMP responsive to GM-CSF or CSF-1 was approximately equal; the number of CSF-1 colonies increased significantly through day 10, while those cultured in GM-CSF did not. The response of BMP to CSF-1 and GM-CSF was also studied in liquid culture; the differences in yield of mature macrophages was consistent with the differences observed in agar culture. Although both cell populations were shown to be 100% mononuclear by day 7, Coulter Channelyzer analysis of these mature macrophages showed marked differences in cell size distribution. By day 7, cells grown in CSF-1 resulted in a homogeneous population of large cells, whereas GM-CSF cultures showed a heterogeneous distribution. Finally, CSF-1-derived cells possessed increased nonspecific and specific phagocytic capabilities when compared to GM-CSF-derived macrophages. These findings indicate that the actions of GM-CSF and CSF-1 upon the bone marrow compartment results in the generation of mature macrophages which differ morphologically and functionally and may account for the heterogeneity in macrophage populations.
D000818:Animals; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor