Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 45

Erythropoietin acts in the bone marrow by a specific erythropoietin receptor
(EpoR) located mainly on erythroid progenitors. It stimulates proliferation of
erythroid progenitors and maintains their viability. More precisely, Epo induces the
proliferation of burst-forming unit-erythroid (BFUe, early erythroid progenitor) and
differentiation of colony-forming unit-erythoid (later erythroid precursor) [ 85 ]. It
also promotes megakaryocyte differentiation, B-cell proliferation, and endothelial
cell chemotaxis. Furthermore, erythropoietin prevents the destruction of viable
tissue surrounding injuries, such as infarction.

2.4.2.3 Thrombopoietin

Thrombopoietin (Tpo) participates in hematopoiesis in general, and thrombopoiesis
in particular (Fig. 2.5 ). Thrombopoietin, assisted by interleukin-11, stimulates the
production of megakaryocytes via myeloid progenitors and, afterward, of platelets
(megakaryocyte fragmentation produces platelets).
Thrombopoietin is manufactured by the liver, kidneys, smooth muscle, and
marrow in particular. It has the longest half-life (30 h) in the circulation among
hematopoietic growth factors.

2.4.2.4 Colony-Stimulating Factors

Colony-stimulating factors (CSF) are cytokines that stimulate the proliferation of
stem cells of the bone marrow in adults.
Granulocyte-monocyte colony-stimulating factor (gmCSF or CSF2) induces the
commitment of granulocyte-monocyte progenitors. It stimulates proliferation of
multi-lineage progenitors and the growth of BFUe, granulocyte, macrophage, and
eosinophil colonies [ 85 ]. It also enhances phagocyte (neutrophil, eosinophil, and
macrophage) functioning. It is secreted by lymphocytes after stimulation by anti-
bodies on the one hand and fibroblasts and endothelial cells activated by IL1 and
TNF produced by macrophages and T cells on the other. Factor gmCSF can also be
synthesized by macrophages and mastocytes.
Granulocyte-macrophage colony-stimulating factor receptor (gmCSFR or
CSF2R) on hematopoietic cells can be activated by gmCSF, and interleukin-3
and -5. It primes the Ras-cRaf-MAPK pathway.
Granulocyte-colony stimulating factor (gCSF or CSF3), produced by endothelial
cells, macrophages, and immunocytes, stimulates the proliferation and maturation
of monopotent neutrophil progenitors that differentiate into neutrophils. It thus has
a relatively specific activity. Further stimulated by IL5, granulocyte-monocyte pro-
genitors develop into eosinophils. It is also produced by fibroblasts, monocytes, and
macrophages stimulated by gmCSF and IL3 cytokines. Interleukin-3 participates
in the differentiation of basophils. Factor gCSF enhances neutrophil functioning
(chemotaxis and phagocytosis) and is involved in neutrophil extravasation.