Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 169

In bones, osteoblasts develop from promonocytes owing to colony-stimulating
factor CSF1. Osteoblasts and osteoblast-derived monocyte-osteoclast progenitors
then differentiate into osteoclasts in response to TNFSF11 receptor. Bone marrow
monocytes and macrophages also arise from promonocytes stimulated by CSF1
factor.
Monocytes that are released into the blood circulation include several
subpopulations; for example, in rodents: Ly6C high (lymphocyte antigen-6 complex),
Ly6C low , and TIE2-expressing monocytes. Ly6C high monocytes differentiate into
inflammation-associated and tissue-resident dendritic cells. Ly6C low monocytes
differentiate into tissue-resident macrophages, inflammatory macrophages (or
M1 macrophages) at sites of infection and injury, and alternatively activated
macrophages (or M2 macrophages) in response to parasitic infection or allergic
condition and during tissue repair. TIE2-expressing monocytes give rise to TIE2 +

macrophages that are involved in tumoral angiogenesis.

3.13.2.3 Macrophage Types

Macrophages exhibit functional flexibility, as they change their activity in response
to environmental signals and give rise to distinct cellular populations. Macrophages
can be classified based on cell-specific biochemical markers as M1 cells 177 and
M2 cells. 178 However, the M2 population includes macrophages that differ in
expression and function.
Tumor-associated macrophages release growth and angiogenic factors. Tumor-
associated macrophages release tumor-necrosis factor, interleukin-1, IL6, CXC-
chemokine ligand-8, vascular endothelial growth factor, and colony-stimulating
factor-1 (CSF1). Production of reactive nitrogen species after NOS2 stimulation
can drive additional DNA mutations. Immunocyte contribution to tumorigenesis
may depend on the balance between tumor-promoting cytokines (interleukin-6), and
tumor-curtailing cytokines (interleukin-10 and transforming growth factor- ).

Macrophages can also be categorized according to their markers (Table 3.41 ),
main

β

function, and activation mode: (1) host defense ( classically activated

and tumor-necrosis factor stimulation; 179
(2) wound healing ( non-classically targeted macrophages or alternatively activated

macrophages ) upon interferon- γ

177 M1

cells produce interleukin-12, granulocyte-macrophage colony-stimulating factor,

interferon- , and tumor-necrosis factor.

178 M2 cells secrete interleukin-10, transforming growth factor-

γ

β , vascular endothelial growth

factor, and inducible nitric oxide synthase (iNOS or NOS2) [ 309 ].
179 Interferon- γ synthesized by helper-1 T cells or CD8 + T cells creates in synergy with tumor-
necrosis factor released by antigen-presenting cells classically activated macrophages that secrete
interleukins IL1, IL6, IL12, and IL23 [ 299 ]. Interferon- γ is transiently produced by natural killer
cells. A sustained population of activated macrophages requires Ifn

γ

synthesis by helper-1 T cells.

β γ

TLR ligands can also cause Ifn production to replace Ifn .