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).
