The monocyte is a spherical cell with prominent surface ruffles and blebs when examined by scanning electron microscopy. As the monocyte enters the tissue and differentiates into a macrophage, the cell volume and number of cytoplasmic granules increase. Cell shape varies, depending on the tissue in which the macrophage resides (e.g., lung, liver, spleen, brain). A characteristic feature of macrophages is their prominent electron-dense membrane-bound lysosomes, which can be seen fusing with phagosomes to form secondary lysosomes. The latter contain ingested cellular and noncellular material in different stages of degradation. A broad range of surface receptors for many ligands, including the Fc portion of immunoglobulin, complement proteins, cytokines, chemokines, lipoproteins, and others, are on the cell surface. Macrophages differ in appearance, biochemistry, and function based on the environment in which they mature from monocytes. These differences are exemplified by the diversity among dendritic cells of lymph nodes, histiocytes of connective tissue, osteoclasts of bone, Kupffer cells of liver, microglia of the central nervous system, and macrophages of the serosal surfaces, each fashioned to meet the local needs of the mononuclear phagocyte system, which plays a role in inflammation and host defense against microbes. Modern cell biologic methods refined our knowledge of surface receptors, endocytosis, and lysosomal degradation, with emphasis on membrane flow and secretion. These pioneering studies culminated in the discovery of dendritic cells as potent, specialized antigen-presenting cells. Subsequent development of monoclonal antibodies 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.
Acronyms and Abbreviations
APC, antigen-presenting cell; CD, cluster of differentiation; CR, complement receptor; CSF, colony-stimulating factor; 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; FcR, Fc receptor; GM-CSF, granulocyte-monocyte colony-stimulating factor; GPCR, G-protein–coupled receptor; HLA, human leukocyte antigen; IBD, inflammatory bowel disease; IFN, interferon; Ig, immunoglobulin; IL, interleukin; IMP, intramembrane particle; IRAK, interleukin receptor-associated kinase; LFA, lymphocyte function–associated antigen; LPS, lipopolysaccharide; m-ϕ, macrophage; MARCO, macrophage receptor with collagenous structure; M-CSF, macrophage colony-stimulating factor; MHC, major histocompatibility complex; MPO, myeloperoxidase; NF, nuclear factor; NLR, NOD-like receptor; NOD, nucleotide-binding oligomerization domain; PI3K, phosphatidylinositol 3-kinase; PS, phosphatidylserine; SR, scavenger receptor; TGF, transforming growth factor; TLR, toll-like receptor.
MONONUCLEAR PHAGOCYTE SYSTEM OVERVIEW
Modern study of mammalian phagocytes began with Metchnikoff in the 19th century. An understanding of the ontogeny, kinetics, and function of phagocytic cells in animals led to the concept of the mononuclear phagocyte system.1,2 Kinetic studies indicate that marrow monoblasts and monocytes develop from the common myeloid progenitor, a derivative of the hematopoietic stem cell, ...