Haemopoietic Growth Factors
The haemopoietic growth factors are glycoprotein hormones that regulate the proliferation and differentiation of haemopoietic progenitor cells and the function of mature blood cells. They may act locally at the site where they are produced by cell–cell contact or circulate in plasma. They also bind to the extracellular matrix to form niches to which stem and progenitor cells adhere. The growth factors may cause cell proliferation but can also stimulate differentiation, maturation, prevent apoptosis and affect the function of mature cells (Fig. 1.5).
They share a number of common properties (Table 1.2) and act at different stages of haemopoiesis (Table 1.3; Fig. 1.6). Stromal cells are the major source of growth factors except for erythropoietin, 90% of which is synthesized in the kidney, and thrombopoietin, made largely in the liver. An important feature of growth factor action is that two or more factors may synergize in stimulating a particular cell to proliferate or differentiate. Moreover, the action of one growth factor on a cell may stimulate production of another growth factor or growth factor receptor. SCF and FLT3 ligand (FLT3‐L) act locally on the pluripotential stem cells and on early myeloid and lymphoid progenitors (Fig. 1.6). Interleukin‐3 (IL‐3) and granuloctye–macrophage colony‐stimulating factor (GM‐ CSF) are multipotential growth factors with overlapping activities. G‐CSF and thrombopoietin enhance the effects of SCF, FLT‐L, IL‐3 and GM‐CSF on survival and differentiation of the early haemopoietic cells.
These factors maintain a pool of haemopoietic stem and progenitor cells on which later‐acting factors, erythropoietin, G‐CSF, macrophage colony‐stimulating factor (M‐CSF), IL‐5 and thrombopoietin, act to increase production of one or other cell lineage in response to the body’s need. Granulocyte and monocyte formation, for example, can be stimulated by infection or inflammation through release of IL‐1 and tumour necrosis factor (TNF) which then stimulate stromal cells to produce growth factors in an interacting network (see Fig. 8.4). In contrast, cytokines, such as transforming growth factor‐β (TGF‐β) and γ‐interferon (IFN‐γ), can exert a negative effect on haemopoiesis and may have a role in the development of aplastic anaemia (see p. 244).