Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 175

Myeloid-derived suppressor cells are also activated by the JaK1-STAT1 and -
STAT6 signaling, the JaK3-STAT6 pathway, as well as Toll-like receptor-mediated
activation of nuclear factor- B. Calcium-binding proteins S100A8 and S100A9

stimulated by STAT3 bind to the NADPH oxidase complex that generates reactive
oxygen species. Signal transducers and activators of transcription STAT1, STAT3,
and STAT6 upregulate production of arginase-1, NOS2, and TGF

κ

β ,aswellas

survival agents, such as MyC, BCLxL, and cyclin-D1.
Once activated, myeloid-derived suppressor cells are characterized by an in-
creased production of nitric oxide and reactive oxygen and nitrogen species, as
well as heightened activity of arginase-1 191 and inducible nitric oxide synthase
(NOS2) [ 316 ]. Both ROS and NO are involved in the suppressive function of
myeloid-derived suppressor cells. Furthermore, myeloid-derived suppressor cells
are able to induce development of FoxP3 regulatory T cells.

In humans, myeloid-derived suppressor cells have a CD33

+

+ or CD11b + ,

phenotype. 192 Myeloid-derived suppressor cells lack expression of
markers of mature myeloid and lymphoid cells and MHC class-2 HLADR molecule.
They have also been detected within a CD15

CD14 − ,CD33 +

+ population in human peripheral

blood.
Two subsets of myeloid-derived suppressor cells exist according to morphology
and plasmalemmal molecule expression. In mice, the granulocytic subset has
a CD11b , Ly6C low

+ , Ly6G + phenotype, whereas the monocytic subset has a

,LY6C high phenotype [ 316 ]. 193 Several other surface molecules
identify additional subsets of myeloid-derived suppressor cells, such as CD80,
CD115 (CSF1R), and CD124 (IL4

CD11b + ,LY6G −

α chain).

191 Arginase-1 that is encoded by the ARG1 gene converts L arginine to urea and L ornithine.
192 CD11b is also designated as

α M -integrin. Molecule CD33 is a common myeloid marker.
193 In mice, markers lymphocyte antigen-6 complex Ly6G and Ly6C that are encoded by different
genes are antibody epitopes specific for the myeloid cell lineage differentiation antigen anti-
granulocyte receptor-1 (GR1) that binds to Ly6G on neutrophils and to Ly6C on neutrophils,
dendritic cells, and subpopulations of lymphocytes and monocytes. The GR1 antigen, or RB6-8c5,
was subsequently identified as a member of the Ly6 gene set. Myeloid cell immunophenotyping in
mouse spleen relies on markers, such as CD11b, CD11c, Gr1, Ly6C, and Ly6G to identify various
splenic cell myeloid populations. Both Ly6G and Ly6C markers are better than GR1 for the iden-
tification of splenic neutrophils, eosinophils, and subsets of monocytes and macrophages [ 317 ].