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252 R. Okamoto et al.

(MEP) and granulocyte-macrophage progenitors (GMP). The MEP eventually
differentiates into functional red blood cells and platelets. The GMP gives rise to
mature mast cells, eosinophils, neutrophils, and monocytes/macrophages. The CLP
population produces either mature T or B lymphocytes (Fig. 11.1).
The differentiation and proliferation of hematopoietic stem cells, as well as, their
more mature precursor cells are highly controlled by stimulation of cytokines from
the extracellular environment. Each of these stem cells has cell surface receptors for
specific cytokines. Binding of cytokines to these receptors stimulates secondary
intracellular signals that deliver a message to the nucleus to enhance proliferation,
differentiation, and/or activation. The growth factors acting primarily on the
granulocyte-macrophage pathway are granulocyte-macrophage colony-stimulating
factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage
colony-stimulating factor (M-CSF). The GM-CSF also stimulates eosinophils,
enhances megakaryocytic colony formation, and increases erythroid colony
formation in the presence of erythropoietin (Epo). In vivo, the cytokine causes an
increase in granulocytes, monocytes, and eosinophils. The GM-CSF can activate the
monocytes and granulocytes to kill efficiently invading microbes. The G-CSF stimu-
lates the formation of granulocyte colonies in vitro. It is able to act synergistically

RCP Red blood cell
MEP
MeP Megakaryocyte/
Platelet

CMP MCP Mast cell

EoP Eosinophil
GMP
NeP Neutrophil
HSC
Monocyte /
MoP
Macrophage

PreT T lymphocyte
CLP
PreB B lymphocyte
Fig. 11.1 Scheme of hematopoiesis. HSC hematopoietic stem cell, CMP common myeloid
progenitor, CLP common lymphoid progenitor, MEP megakaryocyte-erythroid progenitor, GMP
granulocyte-macrophage progenitor, RCP red blood cell precursor, MeP megakaryocyte precur-
sor, MCP mast cell precursor, EoP eosinophil precursor, NeP neutrophil precursor, MoP mono-
cyte-macrophage precursor, PreT precursor of T lymphocyte, PreB precursor of B lymphocyte