Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 170

macrophages ) upon interleukins IL4 and IL13 excitation; 180 and (3) immune
regulation (regulatory macrophages) upon activation by immune complexes,
prostaglandins, G-protein-coupled receptor ligands, glucocorticoids, apoptotic cells,
or interleukin-10 [ 299 ]. 181
Classically activated macrophages produced during cell-mediated immune re-
sponses have microbicidal and tumoricidal activity. The non-classically targeted
macrophage family comprises wound-healing macrophages. Regulatory macro-
phages produce high IL10 level to suppress immune responses. Macrophages
adapt their activity to innate and adaptive immune responses. Endogenous stimuli
generated by innate immunocytes after injury or infection exert a strong, transient
effect on macrophages. On the other hand, prolonged signals produced by antigen-
specific immunocytes induce long-term changes in macrophages.

3.14 Dendritic Cells

Dendritic cells can differentiate from tissue-resident progenitors, such as bone
marrow-derived myeloid precursors, or blood monocytes. Therefore, monocytes
differentiate not only to macrophages, but also dendritic cells.
Dendritic cells are major antigen-presenting cells. They collect and process
exogenous antigens in peripheral tissues. After exposure to antigen, they enter
lymphatic vessels and migrate to lymphoid organs to present antigen to and activate
CD4 T lymphocytes against these antigens. 182 Immature and mature

dendritic cells possess a high phagocytic activity and high cytokine-producing
capacity, respectively.

+ and CD8 +

180 Interleukin-4 and/or -13 are produced by helper-2 T cells that are primarily stimulated
in disturbed mucosal layers [ 299 ]. Basophils and mastocytes are important early sources of
IL4 production. Interleukin-4 stimulates arginase activity in macrophages to convert arginine
into ornithine, a precursor of polyamines and collagen. These macrophages not only secrete
components of the extracellular matrix, but also indirectly regulate the immune response because
polyamines can influence cytokine synthesis. In addition, wound-healing macrophages synthesize
resistin-like molecule RELM

α

.
181 Regulatory macrophages dampen the immune response and inflammation during later stages
of adaptive immune responses. Many types of regulatory macrophages express high levels
of costimulatory molecules CD80 and CD86 and can present antigens to T lymphocytes.
All regulatory macrophage subpopulations need 2 stimuli to prime anti-inflammatory activity.
Interleukin-10 produced by regulatory T cells generates a population of regulatory macrophages
that act as antigen-presenting cells, produce immunosuppressive IL10, reduce IL12 expression,
and can expand helper-2 T-cell population. Glucocorticoids released by adrenal cells can impede
macrophage-mediated host defense and inflammation, but not phagocytosis of apoptotic cells.
182 In inflammatory sites, dendritic cells upregulate homing CCR7 receptors. They can then enter in
draining lymph vessels that express the CCR7 ligands, CCL19 and CCL21 chemokines. In lymph
nodes, antigen-loaded dendritic cells activate immature T cells that migrate to the inflammation
site.