Biology and mechanisms of action of synergistically stimulated myeloid progenitor cell proliferation and suppression by chemokines

A number of cytokines can act together to stimulate/enhance the proliferation of hematopoietic stem and progenitor cells in a greater than additive fashion. An example of this is the combination of a colony-stimulating factor with a potent costimulating molecule such as steel factor. Certain members of the chemokine family of cytokines can suppress this synergistically enhanced proliferation. This review focuses on cytokines involved in these stimulating/enhancing/suppressing effects with regard to biological activity and what is beginning to be learned about the intracellular signal transduction events that mag be mediating these effects. Examples of intracellular mediators involved include, but are not limited to, the Raf-1/MAP kinase pathway and cyclin-dependent kinase inhibitors p21(cip-1) and p27(kip-1) for cell proliferation, and eukaryotic initiation factor-4E and 4E binding protein 1 for protein synthesis.