Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 162

Blood monocytes, many macrophage subsets, and most dendritic cells originate
from common myeloid (CMP), granulocyte-macrophage (GMP), and monocyte-
macrophage-dendritic cell (MDP) progenitor and precursor cells. 169 In humans,
like all lymphoid cell types, myeloid lineages — monocytes, macrophages and
dendritic cells — originate from multilymphoid progenitors, a distinct population
of Thy1 neg / low (thymocyte differentiation antigen-1 or CD90), CD45 + cells of the

CD34 stem cell compartment [ 293 ].

Monocytes are circulating precursors for tissue macrophages and dendritic cells.
However, many types of dendritic cells and macrophages, such as dendritic cells
of lymphoid organs, plasmacytoid dendritic cells, cutaneous Langerhans cells, and
brain microglial cells, originate from the common monocyte, macrophage, and
dendritic cell precursor independently of monocytes [ 294 ]. Although inflammatory
monocytes with the GPI-anchored myeloid differentiation marker lymphocyte
antigen-6 complex, locus G (Ly6G in mice), i.e., Ly6G

+ ,CD38 −

, Ly6C1 high monocytes,
generate macrophages and dendritic cells, many types of dendritic cells and macro-
phages do not originate from monocytes in normal condition [ 301 ]. Furthermore, in
some cases, they can develop independently of the bone marrow.
The generation of monocytes, macrophages, and to some extent, dendritic cells
depends on cytokine and hematopoietic growth factor receptor CSF1R expressed
exclusively on mononuclear phagocytes (monocytes and macrophages) and their
precursors [ 296 ]. Known CSF1R ligands include CSF1 170 and interleukin-34.
Colony-stimulating factor-1 contributes to the control of survival, proliferation,
and differentiation of mononuclear phagocytes. Liganded receptor protein Tyr
kinase CSF1R stabilizes and provokes the nuclear translocation of

+

-catenin that
activates genes involved in the cell cycle. 171 Activity of CSF1 relies on its associated
adaptor, protein Tyr kinase-binding protein TyroBP that, once phosphorylated,
acts as a docking site for spleen Tyr kinase (SYK) and 70-kDa TCR

β

-chain-
associated protein kinase (ZAP70), and leads to phosphorylation of glycogen
synthase kinase GSK3

ζ

β [ 297 ]. Owing to TyroBP, calcium-dependent focal adhesion

kinase-2 phosphorylates β -catenin that then accumulates in the nucleus.

3.13.1 Monocytes

Monocyte (Mo; size 15-25 m) is the largest leukocyte. Its nucleus is most often

U- or bean-shaped. These bone marrow-derived circulating leukocytes account for
3-9% of all leukocytes.

169 In humans, hematopoietic stem cells are associated with the Lin

com-
partment [ 293 ]. In adults, hematopoietic stem cells and precursors recirculate between peripheral
organs and the bone marrow.
170 A.k.a. macrophage colony-stimulating factor.
171 Liganded CSF1R dimerizes, autophosphorylates, and signals via phosphorylation of PTPn1
phosphatase and PLC

− ,CD34 + ,CD38 −

, as well as Src, PI3K, PKB, and ERK kinases. The CSF1-CSF1R complex
is subsequently internalized and degraded in lysosomes.

γ