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 (eg, lymph node, lung, liver spleen, brain). A characteristic feature of macrophages is their prominent electron-dense membrane-bound lysosomes, which fuse 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 play a major role in innate as well as adaptive immunity. Macrophages differ in appearance, biochemistry, and function based on the environment in which they mature from embryonic cells or circulating 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 CNS, 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 have advanced our knowledge of the surface proteins and mechanisms of endocytosis and lysosomal degradation of macrophages. These studies, in turn, have resulted in the discovery that dendritic cells are potent, highly specialized antigen-presenting cells. Subsequent development of monoclonal antibodies and molecular cloning of surface proteins and cytokines, followed by microarray analysis and single cell omics, provided the sensitive and specific tools which enabled the analysis of monocyte/macrophage functions in vitro and in vivo, bringing important insights into their cytotoxic and antimicrobial activities and their tropic and homeostatic functions.
MONONUCLEAR PHAGOCYTE SYSTEM
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, and that tissue macrophages develop from monocytes that have migrated from the blood pool in response to chemotactic stimuli (Table 67–1 and Chap. 18). Tissue macrophages share many functional characteristics, such as phagocytic and microbial killing capabilities and adherence to glass or plastic surfaces in vitro. Vascular endothelium, reticular cells, and dendritic cells of lymphoid germinal centers usually are not included in the mononuclear phagocyte system, although the now obsolete term reticuloendothelial system3 denoted cells as playing some complementary part with mononuclear phagocytes. In addition to developing the multitude of types of tissue macrophages, monocytes can differentiate into myeloid-derived dendritic cells.4,5
TABLE 67–1.Distribution of Mononuclear Phagocytes