CONCEPTS OF HEMATOPOIETIC-CELL AMPLIFICATION, SYNERGY, REDUNDANCY ANDPLEIOTROPY OF CYTOKINES AFFECTING THE REGULATION OF ERYTHROPOIESIS

Hemopoietic cell amplification in vivo is regulated by various mechani sms which appear to be under control of many hemopoietic growth factor s. Quiescent stem cells can be activated into cell cycle, dividing pro genitor cells can reduce their cell cycle time, the differentiation ve locity (i.e. transit-time) can be manipulated, apoptosis can be preven ted, and finally, at least in the murine system, migration of cells be tween the microenvironments in marrow and spleen may take place. Pertu rbations of any of the parameters by which these mechanisms are define d, will affect in vivo blood cell production. In this review the conse quences of these perturbations, and the role of growth factors herein, are discussed. These fundamental aspects of the regulation of hemopoi esis are illustrated with recent data showing the synergistic, redunda nt and pleiotropic effects of SCF, IL-11, EPO and G-CSF on the in vivo formation of erythrocytes. Given the overwhelming number of growth fa ctor-related studies that are now appearing, a re-evaluation of data, available in the literature, in the context of the mechanistic approac h of growth factor-dependent hemopoiesis which is presented in this pa per, seems to be useful and warranted.