The colony-stimulating factors and XXXX .

@entity6542 @entity2304 @entity1 @entity9827 @entity19 @entity24778 @entity5 @entity1778
The production of granulocytes and macrophages is under the control of at least four well defined haemopoietic growth factors or colony-stimulating factors (CSF's) which differ in their actions within the hierarchical organization of haemopoietic progenitor cells and in the different cell lineages they affect. Multi-CSF has an extremely broad @entity6542 , @entity2304 stimulates all granulocyte and macrophage progenitor cells and @entity24778 and @entity9827 have actions essentially restricted to the granulocyte or macrophage cell lineages, respectively. They are each, however, required for cell survival, proliferation, differentiation and mature cell activation within the cell lineages they act on. They each exert their actions through specific high-affinity cell surface receptors which show no direct cross reactivity with each other and which are structurally distinct. However, at physiological temperatures the CSF's show a specific pattern of receptor co-down-modulation which might reflect their cell lineage specificities. A major defect in @entity1778 is a block to differentiation so that cell divisions result in self-renewal of the leukaemic stem cells rather than terminal differentiation to non-dividing cells. In @entity19 models such a defect does not result in @entity5 until it is accompanied by autonomy from external CSF growth control but in @entity1 @entity1778 there is no evidence for autonomy from CSF growth control and CSF's may play a permissive role in the emergence of @entity1778 . The possibility of using CSF's to override the differentiation block in @entity1778 and cause suppression of leukaemic growth by differentiation induction has been examined for the action of @entity24778 on @entity19 leukaemic WEHI-3B D+ cells. @entity24778 induces differentiation in these cells, strongly suppresses cell divisions leading to self-renewal and increases the survival time of @entity19 injected with treated cells. The possible importance of this factor in cell differentiation is indicated by the loss of @entity24778 receptors in a differentiation-defective mutant of WEHI-3B, the conservation of @entity24778 and its receptor from @entity19 to @entity1 and the observation that all primary @entity1 @entity1778 exhibit specific receptors for this factor.
