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Monocytes and macrophages play an important role in hematology, both as a component of the hematopoietic system and within the stroma and tissue microenvironment where they contribute trophic and clearance functions. They constitute a widely dispersed cellular system throughout the body, interacting with host cells and foreign invaders through their versatile biosynthetic and secretory responses, to maintain physiologic homeostasis. They are specialized migratory or sessile phagocytes, present within the circulation and extravascular tissue compartment, contributing to diverse hematologic diseases, directly and by production of bioactive products. Because of extensive heterogeneity and plasticity, their centrality has not always been recognized by hematologists. The origin, life span, and functions of the monocyte are the focus of this chapter, including their relevance to hematologic health and disease in humans, based on current understanding of their properties. The relationship of monocytes and macrophages to dendritic cells, and monocyte-derived cells with a specialized immunologic role in T-lymphocyte activation, are described. Together, macrophages and dendritic cells are major antigen-presenting cells, contributing to host defense, innate and acquired immunity, and inflammation, as well as noninfectious disease processes, both within and outside the lymphohematopoietic organs.

Acronyms and Abbreviations

Abbreviations and acronyms that appear in this chapter include: CR, complement receptor; DC, dendritic cell; DC-SIGN, dendritic cell-specific intercellular adhesion molecule-3–grabbing nonintegrin; EMR, epidermal growth factor module-containing mucin-like hormone receptor; FACS, fluorescence-activated cell sorting; FcR, Fc receptor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN-γ, interferon-γ; IL, interleukin; LPS, lipopolysaccharide; MARCO, macrophage receptor with a collagenous structure; M-CSF, macrophage colony-stimulating factor; M-CSFR, macrophage colony-stimulating factor receptor; MR, mannose receptor; Sn, sialoadhesin; SR-A, scavenger receptor A; TGF, transforming growth factor; TLR, toll-like receptor; TNF-α, tumor necrosis factor-α.

The history1 and nomenclature of the family of macrophages and closely related cells have been reviewed extensively. We refer to the mononuclear phagocyte system (MPS), collectively, and consider macrophage heterogeneity in different tissue compartments in detail. Aspects of their morphology and contribution to clinical conditions are found in Chap. 68. This chapter deals with the basic cellular and molecular properties of monocytes and macrophages in general, as well as more specifically within the hematopoietic system. There are many useful texts and reviews available for further study; a selection is found in the references section of this chapter and Chap. 68.2–6 A recent set of recorded lectures on relevant topics is available from Henry Stewart Talks.7

Our current knowledge is based on long-standing methods of intravital labeling with carbon or carmine; in situ phenotyping with gene expression analysis and immunocytochemistry (antigen markers); cell isolation and characterization (fluorescence-activated cell sorting [FACS]); and in vitro culture (colony growth in semisolid media, and liquid cultures with or without growth factors and cytokines) of cells obtained from fetal liver, marrow, and spleen. Peritoneal macrophages harvested from unstimulated mice or after injection of inflammatory stimuli such as thioglycollate broth and Biogel polyacrylamide beads have been particularly useful.8,9 More complex ...

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