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From the earliest observations by Elie Metchnikoff on phagocytosis and intracellular digestion of microbes and damaged cells by macrophages of invertebrates and higher organisms, their scavenging and host defense functions have been of major interest. In the 1960s Cohn and his colleagues introduced modern cell biologic methods to refine our knowledge of surface receptors, endocytosis, and lysosomal degradation, with emphasis on membrane flow and secretion.1 These pioneering studies culminated in the discovery of dendritic cells (DCs) as potent, specialized antigen-presenting cells (APCs).2–3 Subsequent development of monoclonal antibodies4 and molecular cloning of surface proteins and cytokines, followed by microarray analysis and genomics, provided the sensitive and specific tools to analyze macrophage functions in vitro and in vivo. These studies have brought insights into macrophage cytotoxic and antimicrobial activities and, to a lesser extent, their trophic, homeostatic functions in the body. Macrophages play a major role in innate as well as adaptive immunity. An important issue is that of heterogeneity among and within monocyte and macrophage populations, as discussed in Chap. 69, which also deals with their growth and differentiation.5 This chapter focuses on the molecular and cellular properties that bear on the versatile functions of monocytes and macrophages, overlapping in part with the specialized functions of DCs and osteoclasts. General and selected references are provided in recent volumes,6–8 including Chap. 69.

Acronyms and Abbreviations

Abbreviations and acronyms that appear in this chapter include: Ag, antigen; APC, antigen-presenting cell; CD, cluster of differentiation; CR, complement receptor; DC, dendritic cell; EGF, epidermal growth factor; EGF-TM7, epidermal growth factor-seven transmembrane; EMR2, epidermal growth factor-like module containing mucin-like hormone receptor-like 2; ER, endoplasmic reticulum; FcR, Fc receptor; GPCR, G-protein-coupled receptor; IBD, inflammatory bowel disease; ICE, interleukin 1-converting enzyme; IFN, interferon; IFN-αR, IFN-α receptor; IFN-γR, IFN-γ receptor; Ig, immunoglobulin; IL, interleukin; IPAF, ICE-protease activating factor; IRAK, interleukin receptor-associated kinase; IRF, IFN regulatory factor; JAK, Janus kinase; LFA, lymphocyte function-associated antigen; LPS, lipopolysaccharide; MARCO, macrophage receptor with collagenous structure; MPO, myeloperoxidase; MR, mannose receptor; NACHT, domain present in NAIP, CIITA, HET-E, and TP-1; NAIP, neuronal apoptosis inhibitor protein; NALP, NACHT leucine-rich repeat protein; NF, nuclear factor; NLR, NOD-like receptor; NOD, nucleotide-binding oligomerization domain; PI, phosphatidylinositol; PIP3, phosphatidylinositol 3,4,5 phosphate; PI3K, phosphatidylinositol 3 kinase; PS, phosphatidylserine; SH2, Src homology 2 domain; SR, scavenger receptor; STAT, signal transducers and activator of transcription; TAP, transporter for antigen processing; TLR, toll-like receptor; WASP, Wiskott-Aldrich syndrome protein.

This section describes specifically monocytic functions and those expressed in common with their differentiated progeny, macrophages, also covering properties of surface molecules with a clear intravascular function. Their immunomodulatory functions can be expressed directly, or after differentiation of precursors to dendritic cells (DCs). Monocytes respond to activating signals, for example, chemokines, through chemokine receptors, setting in motion a series of adhesion and migration events associated with diapedesis.9 They play a direct role in sepsis and in more poorly defined ...

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