Normal human granulomonocytic bone marrow progenitor cells responsiveness to colony-stimulating activity (CSA)
Charbord, P.; Neel, H.; Lehn, P.; Parmentier, C.
Nouvelle Revue Francaise d'Hematologie 22(4): 357-370
1980
ISSN/ISBN: 0029-4810 PMID: 6973142 Document Number: 161767
Responsiveness of granulomonocytic progenitor cells to colony-stimulating activity (CSA) contained in placental conditioned medium was studied in 5 cases of normal human bone marrow. In 3 cases the dose-effect relationship was determined for different seeded cell concentrations and in 1 case for 2 incubation durations (8 and 10 days). For microcluster (2-19 cells) the relationship passed through a maximum obtained for low concentrations of CSA (0.8-1.6%). For clones containing more than 19 cells a plateau was observed for CSA concentrations of more than 8%. A cumulative log-normal distribution fitted the curves describing clone (> 19 cells) vs. CSA concentrations. The variation of 3 parameters characterizing the curves was studied: the level of the plateau, the shape of the curve and the number of clones observed in the absence of conditioned medium. The level of the plateau varied with different seeded cell concentrations and passed through a steady maximum value obtained for several successive CSA concentrations. For an incubation duration of 10 days, the shape of the curves varied with increasing seeded cell concentrations, from a sigmoid to a hyperbola; a Hill representation of the data made it possible to quantify the variation in shape, the Hill coefficient (n) varying from 3.5 (sigmoid) to 1 (hyperbola). For 8 days of incubation, the variation was less marked in 1 case (n = 2.1-1.5) or absent in another (n = 2.2). Using the log-normal distribution, the equivalent CSA concentration, which would account for the clones observed in the absence of placental conditioned medium, was calculated: values were less than or equal to 0.5%, even for more than 2 .times. 105 seeded cells. A model, where the interaction between a receptor on progenitor cells and stimulating molecules is similar to that described for allosteric enzymes, seems compatible with the data. The substrate (i.e., the stimulating factor), inhibitors and activators act at the progenitor cell level. Receptors to these molecules present several subunits, at least 2 ligand-binding sites per subunit and 2 conformations, 1 with high affinity for the substrate, allowing the 1st intracellular steps leading to colony formation. An in vitro regulation process at the progenitor cell level is therefore suggested, activators and inhibitors modulating the action of the stimulating factor or substrate.