Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 165

members of the Kr uppel-like factor (KLF2, KLF4-KLF6, and KLF10-KLF11) and
early growth response families [ 302 ].
Colony-stimulating factor-1 promotes the differentiation of macrophages from
circulating monocytes, but additional factors, such as fibronectin and its receptor,
are required for optimal differentiation.

3.13.2 Macrophages

Macrophages are resident phagocytic cells in lymphoid and non-lymphoid tis-
sues. Cells of the phagocytic lineage differentiate into many different types of
macrophages. Specialized macrophage types include alveolar macrophages in
lung alveoli, microglial cells in the central nervous system, osteoclasts in bones,
histiocytes in connective tissues, Kupffer cells in liver, metallophilic macrophages
in spleen (among other types), as well as dendritic cells (Table 3.39 ). Macrophages
are equipped with numerous pathogen-recognition receptors that are used for
phagocytosis.
In macrophages, endocytosis, i.e., receptor-mediated pinocytosis and non-
specific internalization of substrates via micro- or macropinocytosis (fluid-phase
pinocytosis) as well as phagocytosis , contributes to the immune response.
Mannose receptor-mediated endocytosis yields uptake of numerous mannosylated
glycoproteins and phagocytosed particles.

3.13.2.1 Macrophage Production and Action

Macrophages synthesize growth factors, among which are inflammatory cytokines.
On the other hand, cytokines secreted by activated T cells regulate endocytosis in
macrophages. Interleukin-4 and -13 promote tubular vesicle formation underneath
the plasma membrane and at pericentriolar sites, but reduce vesicle sorting to
lysosomes [ 303 ]. Whereas IL4 and IL13 enhance fluid-phase pinocytosis and
mannose receptor-mediated uptake by activation of phosphatidylinositol 3-kinase,
interferon-

favors
vesicle sorting to perinuclear lysosomes, whereas IL10 attenuates this event [ 303 ].
Macrophages operate in immunity, apoptotic-cell clearance, wound healing, and
tissue development. Macrophages actually are involved in branching morphogen-
esis (e.g., in pancreas and mammary glands), neuronal patterning, angiogenesis,
bone morphogenesis, as well as adipogenesis, and development and growth of
myocytes [ 304 ]. Macrophages also promote malignancy, as they enhance tumor
growth and invasive capacity as well as stimulate angiogenesis.
Macrophages not only operate as immune effectors, but also have homeo-
static roles independent of other immunocytes. Macrophages indeed process dead
erythrocytes and recycle iron and hemoglobin. Red pulp macrophages actually

γ as well as interleukin-10 diminish these processes. Interferon- γ