Interactions of CSFs and cytokines during haematopoiesis

GM-CSF and IL-3 have been shown to compete for receptors in some types of cells (e.g. eosinophils and KG-1 cells), indicating some structural homology between GM-CSF and IL-3 receptors, perhaps because they share certain subunits or adapter proteins. GM-CSF occupancy results in phosphorylation of certain proteins, and because the receptor possesses no inherent kinase activity, receptor occupancy must be linked to kinase activity via the generation of second messenger molecules. Pretreatment of cells with pertussis toxin abolishes the effects of GM-CSF, indicating the involvement of G-proteins in signal transduction. Priming of neutrophil functions with GM-CSF involves the activation of phospholipases A2 and D. 

Whilst the individual CSFs described above can all affect haematopoiesis by acting alone on different types of stem or progenitor cells, they are much more potent when they act together on a particular cell type. Such synergis- 

Other cytokines also appear to be involved in the regulation of haematopoiesis, but it is difficult to assess if these directly affect the activities of stem and progenitor cells. Alternatively, they may mediate their effects via the stimulation of stromal cells to secrete a secondary factor that is then actually responsible for the observed effects. Other cytokines implicated in stimulation of haematopoiesis include the following  

which has no proliferative effect when acting alone but modulates the responses of haematopoietic cells to other CSFs (possibly by enhancing CSF-receptor expression), enhances the differentiation and survival of early progenitor cells observed in response to IL-3 and stimulates the production of G- and GM-CSF by T lymphocytes, endothelial cells, macrophages and fibroblasts  

which has no effect alone but enhances the proliferative response to G- and GM-CSF, whilst inhibiting the responsiveness to IL-3  

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