The macrophage (Fig. 1) and its precursors are widely distributed throughout the body. These cells constitute a physio logic system, the mononuclear phagocyte system (previously referred to as the reticuloendothelial system), which includes promonocytes and their precursors in the bone marrow, monocytes in the circulating blood, and macrophages in tissues. This collection of cells is considered to be a system because of the common origin, similar morphology, and shared functions, including rapid phagocytosis mediated by receptors for IgG and the major fragment of C3.

Fig1. lectron micrograph of a macro phage. (From Barrett JT: Textbook of immunology, ed 5, St Louis, 1988, Mosby.)

Macrophages and monocytes  migrate freely into the tissues from the blood to replenish and rein force the macrophage population. Cells of the macrophage system originate in the bone marrow from the multipotential stem cell. This common committed progenitor cell can differentiate into the granulocyte or monocyte-macrophage path way, depending on the microenvironment and chemical regulators. Maturation and differentiation of these cells may occur in various directions. Circulating monocytes may continue to be multipotential and give rise to different types of macrophages.

Macrophages exist as fixed or wandering cells. Specialized macrophages such as the pulmonary alveolar macrophages are the so-called dust phagocytes of the lung that function as the first line of defense against inhaled foreign particles and bacteria. Fixed macrophages line the endothelium of capillaries and the sinuses of organs such as the bone marrow, spleen, and lymph nodes. Macrophages, along with the network of reticular cells of the spleen, thymus, and other lymphoid tissues, are organized into the mononuclear phagocyte system (Fig. 2).

Fig2. Mononuclear phagocyte system.  (Adapted from Roitt IM: Essential immunology, ed 5, Oxford, 1984, Blackwell Scientific.)

Functionally, the most important step in the maturation of macrophages is the cytokine-driven conversion of the nor mal resting macrophage to the activated macrophage. Macro phages can be activated during infection by the release of macrophage-activating cytokines such as interferon-gamma (IFN-γ) and granulocyte colony-stimulating factor (G-CSF) from T lymphocytes specifically sensitized to antigens from the infecting microorganisms. This interaction constitutes the basis of cell-mediated immunity. In addition, macrophages exposed to an endotoxin release a hormone, tumor necrosis factor α (TNF-α, cachectin), which can activate macrophages itself under certain in vitro conditions.

The terminal stage of development in the mononuclear phagocyte cell line is the multinucleated giant cell, which characterizes granulomatous inflammatory diseases such as tuberculosis. Both monocytes and macrophages can be shown in the lesions in these diseases before the formation of giant cells, thought to be precursors of the multinucleated cells.

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Monocytes–Macrophages: Host Defense Functions: Phagocytosis

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