Interaction of inhibitor and stimulator in the regulation of CFU-S proliferation.
An inhibitor and stimulator of CFU-S proliferation can be obtained from haemopoietic tissue containing, respectively, relatively quiescent CFU-S (e.g. normal bone marrow) and proliferating CFU-S (e.g. regenerating bone marrow). In this paper we explore the capacity for inhibitor and stimulator production in relation to changes in the proliferative status of the CFU-S and their mode of interaction. The increase in proliferative activity of CFU-S following a concentrated regime of phenylhydrazine injections is paralleled by an increase in the capacity for stimulator production and a decrease in the capacity for inhibitor production. These processes are reversed as the normal low proliferative activity returns. Using density fractionated marrow populations, dose-response measurements show that while inhibitor- and stimulator-producing cells persist throughout the changes in CFU-S proliferation, their magnitude of factor production moderates in relation to those changes. The inhibitor and stimulator are not mutually destructive: the two factors retain their activities after co-incubation and re-separation. On the other hand, the presence of either factor blocks the synthesis of the other by the appropriate producer cells. A model for the regulation of CFU-S proliferation by the inhibitor and stimulator is thus suggested in which the relative spatial distributions of CFU-S in a microenvironment containing inhibitor- and stimulator-producing cells are an important feature. It also implies the existence of a signal from the CFU-S compartment which determines the appropriate inhibitor or stimulator production.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division; D002458:Cell Fractionation; D003470:Culture Media; D006131:Growth Inhibitors / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D008297:Male; D051379:Mice; D010659:Phenylhydrazines / Q000494:pharmacology; D012038:Regeneration
D003470:Culture Media; D006131:Growth Inhibitors; D006133:Growth Substances; D010659:Phenylhydrazines