Mechanism of action of serum factors that regulate granulopoiesis in vitro: possible physiologic role of serum-inhibiting activity

Abstract

The purpose of this study was to investigate mechanisms of action and in vivo relationships of serum factors that regulate granulopoiesis in vitro. Granulopoiesis involves interactions between stimulating and proliferating cells, and in order to determine mechanisms of action it is necessary to assess whether an activity acts on the stimulating or on the proliferating cell. Liquid cultures of monocytes, obtained from light-density white blood cells, were used to observe effects on colony-stimulating factor (CSF) production, and soft agar cultures of nonadherent light-density bone marrow cells were used to determine effects on colony-forming cells. Medium molecular weight serum-stimulating activity increased monocyte CSF production but had no effect on colony-forming cells. High molecular weight serum-inhibiting activity had no effect on CSF production but inhibited the action of CSF. Serum-inhibiting activity correlated with the circulating neutrophil concentration. These observations suggest that serum stimulation of granulopoiesis is achieved indirectly by stimulating marrow CSF-producing cells and that growth of the proliferating cell population is stabilized by a direct negative feedback loop.