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1080 Part VIII: Monocytes and Macrophages Chapter 68: Production, Distribution, and Activation of Monocytes and Macrophages 1081

Tonsil (cryostat)

EMR2
A B C

D E

Figure 68–5. Immunocytochemical detection of macrophages in human (A) and mouse (B to E) lymphohematopoietic tissues. A. Tonsil.
EMR2-positive macrophages are scattered throughout follicles and interfollicular areas. B. Liver. Kupffer cells are F4/80+, unlike sinusoidal endothe-
lium and hepatocytes. C to E. Spleen. C. Red pulp macrophages express F4/80, unlike marginal zone cells. Macrophages in T-cell area are F4/80–,
except for periarteriolar processes. D. Marginal metallophilic macrophages express sialoadhesin (Siglec1) strongly; red pulp macrophages are weakly
positive. E. A subset of marginal metallophils binds a chimeric protein probe of the cysteine-rich domain of the MR-human Fc. For details see Ref. 91.
(A, used with permission from of T. Marafioti. B to E, reproduced with permission from Taylor PR, Zamze S, Stillion RJ, et al: Development of a specific system for
targeting protein to metallophilic macrophages. Proc Natl Acad Sci USA 101(7):1963–1968, 2004.)

clearance of damaged or dying cells and modulating the properties of expressing a reduced killing capacity, as demonstrated for other resident
viable neighboring cells. In sum, these cells provide a homeostatic, tro- macrophage populations.
phic function that is often overlooked in considering their role in cyto- Several monocyte and macrophage populations coexist in the
toxicity and antimicrobial host defense. The properties of macrophages marrow compartment; a network of stromal macrophages, clustered in
in hematolymphoid organs and other tissues, with special relevance to hematopoietic islands, the developing monocytes, as well as osteoclasts
hematologic aspects, are discussed in detail. and isolated macrophages in apposition to bone surfaces. Mature mac-
rophages in human marrow contain prominent inclusions in storage
DISTRIBUTION disorders, such as Gaucher disease and hemosiderosis. Hemophagocy-
tosis, a consequence of perforin deficiency in some patients, and seen in
genetic syndromes and postviral infection, is a striking manifestation of
HEMATOPOIETIC ORGANS excessive macrophage cytopathic activity in the marrow. 57,58 Uptake of
Marrow opsonized platelets by macrophage FcR and CRs in stromal and other
It is often overlooked that mature macrophages are important constitu- resident tissue macrophages are important features of thrombocy-
ents of the hematopoietic stroma, along with fibroblastic mesenchymal topenic syndromes.
56
cells, osteoblasts, and endothelial cells, contributing to hematopoiesis The hematopoietic stem cell lineage which gives rise to monocyte-
beyond their own differentiation (Figs. 68–6A to E and 68–7). Stromal macrophages and myeloid DCs also leads to production of the osteo-
macrophages in hematopoietic island clusters associate with devel- clast lineage. 59,60 Following interaction via Stat4 and RANKL (regulator
oping erythroid and other granulocytic cells through nonphagocytic, of activation of nuclear factor-κB), a member of the superfamily of TNF,
cell–cell adhesion receptors, such as sialoadhesin and a divalent cation- cells undergo differentiation, fusion, attachment to bone as osteoclasts
dependent receptor, as described for fetal liver. The potential trophic and then function in bone remodeling. 61
functions provided by stromal macrophages are ill-defined but include A common marrow progenitor cell that gives rise to both mono-
surface-expressed and secreted growth factors and cytokines. Stromal cytes and DCs has been defined, including both classical DCs and the
20
macrophages are actively endocytic and clear erythroid nuclei and plasmacytoid DCs. 62,63 This common marrow progenitor cell circulates
apoptotic hematopoietic cells as required, rapidly degrading them for in the blood and seeds lymphatic tissues. 62,63 These short-lived, migra-
possible reutilization of iron and other nutrients. Stromal macrophages tory cells modify T-cell responses and, unlike Langerhans cells, are
also interact with less-differentiated hematopoietic precursors through replaced by bloodborne precursors. 41,42 The central activity of imma-
release of potent secretory products, such as IL-1, and with lympho- ture classical DCs is phagocytosis, while that of mature classical DCs is
cytic populations, including plasma cells, through IL-6. They are tar- cytokine production. 62,63
gets for infectious agents, for example, mycobacteria, lentiviruses, and Dendritic cells that occur in lymphoid and nonlymphoid organs
retroviruses, and serve as reservoirs in many chronic infections, while have a major role in processing and presenting antigens, leading to

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