Biomedical Engineering Reference
In-Depth Information
Classical CD14 high ,CD16
monocytes express CCR2 chemokine receptor.
,CD16 high monocytes express higher amounts of MHC class-
2 molecules, low-affinity IgG Fc receptor-2A encoded by the FCGR2A gene
(or CD32), and CCR5 chemokine receptor [ 300 ]. CD14
Non-classical CD14
+
monocytes that respond
to TLR stimuli are involved in inflammation and leukocyte recruitment. CD14
+
+
monocytes can either activate or suppress T-cell responses.
Human CD14 low ,CD16
monocytes sense tissue damage and reply to viruses
and nucleic acids via endosomal TLR7 and TLR8 receptors [ 294 ]. They produce
tumor-necrosis factor, interleukin-1
+
, and CCL3 chemokine.
Another subpopulation of smaller scouting monocytes with longer half-life, the
Ly6G
β
, Ly6C1 low
monocytes, 172
lack CCR2 and L-selectin, but strongly produce
chemokine receptor CX3CR1 and
α L β 2 -integrin [ 301 ].
3.13.1.2
Monocyte Development
Monocytes develop from a common myeloid progenitor cells (i.e., granulocyte-
macrophage colony-forming unit) in the bone marrow in response to macrophage
colony-stimulating factor (Vol. 2 - Chap. 3. Growth Factors and Chap. 2 ). 173
Monocytes are released from the bone marrow into flowing blood and migrate into
tissues to mature into long-lived tissue-specific macrophages (Sect. 3.13.2 ).
During monocyte differentiation into macrophage, lipid and steroid metabolism
changes. Synthesis of Apolipoprotein-C1, -C2, and -E, and lipoprotein lipase
augments [ 302 ]. Production of related enzymes also rises, such as cholesterol 27-
hydroxylase (CyP27a1), acyl coenzyme-A, cholesterol acyltransferase-1 and -2
that esterify cholesterol, 3-hydroxy 3-methylglutaryl coenzyme-A reductase, and
lysosomal phospholipase-A2, as well as that of partners, such as fatty acid-binding
proteins (FABP3-FABP5), scavenger receptors ScaRa, ScaRb2, ScaRd1, and LXR
α
(nuclear receptor NR1H3). Production of some transcription factors also rises, such
as CCAAT/enhancer binding protein-
α
, sprouty homolog-2, interferon regulatory
factor IFR2, and musculoaponeurotic fibrosarcoma homolog (MAF) [ 302 ].
Conversely, certain genes have a decreased activity in macrophages, such as
3 members of the nuclear receptor subfamily 4 (NR4a1-NR4a3) derived from
immediate-early genes, Activator protein-1 components Fos, FosB, JunB, and JunD,
E26 transcription factor ETS2, CCAAT/enhancer binding protein-
δ
, interferon reg-
ulatory factors IRF1 and IRF7, the basic leucine zipper (bZIP) transcription factor
musculoaponeurotic fibrosarcoma proto-oncogene homolog-F (MAFf), FoxO1a and
FoxO3a, Runx1 and Runx3 (AML1 and AML3), SMAD3 and SMAD6, and many
172 In mice, these monocytes do not express murine marker Ly6G, unlike granulocytes, but can be
distinguished by Ly6C marker.
173 This precursor gives rise to many cell types: neutrophils, eosinophils, basophils, monocytes,
macrophages, dendritic cells, and mastocytes.
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