THE RELATIONSHIP BETWEEN DIFFERENT HIGH PROLIFERATIVE POTENTIAL COLONY-FORMING CELLS IN MOUSE BONE-MARROW

Previous work has shown that part of the hierarchical structure of the hematopoietic system can be described by HPP-CFC-1 (primitive high pr oliferative potential colony-forming cells responding to colony-stimul ating factor-1 [CSF-1] + interleukin-3 [IL-3] + IL-1), HPP-CFC-2 (more mature HPP-CFC responding to CSF-1 + IL-3), and mature HPP-CFC respon ding to the single factors, CSF-1, granulocyte-macrophage colony-stimu lating factor (GM-CSF), or IL-3. In this study, we have attempted to r elate the murine HPP-CFC, stimulated by various combinations of growth factors (GFs)-CSF-1, GM-CSF, IL-3, IL-6, IL-1, stem cell factor (SCF) , and transforming growth factor-beta (TGF-beta)-and by CSF-1, GMCSF, and IL-3 on their own, to these known progenitors. Studies involving r egeneration of the bone marrow after 5-fluorouracil (5-FU) treatment, generation of progenitors in liquid cultures in response to different GF combinations, and the HPP-CFC content of lineage-negative rhodamine -sorted bone marrow (BM) fractions have indicated that: 1. the combina tions CSF-1 + IL-3 + IL-1 + SCF and CSF-1 + IL-3 + IL-1 + IL-6, and po ssibly CSF-I + GM-CSF + IL-3 + IL-1, stimulate pre-HPP-CFC-1; 2. the c ombinations CSF-1 + IL-1 + GM-CSF, CSF-1 + IL-1 + IL-6, CSF-1 + IL-1 SCF, CSF-1 + IL-3 + SCF, CSF-1 + IL-6 + SCF, and IL-3 + SCF, appear t o overlap with the CSF-1 + IL-3 + IL-1 combination to stimulate the mo re mature cells of the HPP-CFC-1 compartment; 3. the combinations CSF- 1 + GM-CSF, CSF-1 + IL-1, CSF-1 + IL-6, and CSF-1 + SCF may stimulate the more mature cells of the HPP-CFC-2 population, while the single fa ctors CSF-I, GM-CSF, and IL-3, as suggested in other reports, may stim ulate HPP-CFC that are more mature than the HPP-CFC-2; 4. the combinat ions IL-3 + IL-6 and SCF + IL-6 appear to stimulate HPP-CFC that overl ap with the HPP-CFC-1 population, while those responding to the combin ation GMCSF + TGF-beta overlap with the HPP-CFC-2 population within th e hematopoietic hierarchy; and 5. CSF-1 and GM-CSF appear to be interc hangeable in the combinations studied.