Monocytes, Macrophages, and Dendritic Cells

Development

Monocytes develop more rapidly during bone marrow hematopoiesis and remain longer in the circulation than do neutrophils (see Table 153.1 ). The monoblast is the first recognizable monocyte precursor, followed by the promonocyte , with cytoplasmic granules and an indented nucleus, and finally the fully developed monocyte with cytoplasmic granules filled with hydrolytic enzymes. The transition from monoblast to mature circulating monocyte requires about 6 days.

Three major subsets of human monocytes can be identified on the basis of surface antigens: CD14 ⁺⁺ CD16 ⁻ classical monocytes that constitute the majority of total monocytes in the resting state; the more mature CD14 ⁺⁺ CD16 ⁺ proinflammatory ( intermediate ) monocytes, which produce proinflammatory hormone-like factors termed cytokines , such as tumor necrosis factor-α (TNF-α), in response to microbial stimuli; and nonclassical ( regulatory) monocytes (CD14 ⁺ CD16 ⁺⁺ ) that promote wound healing. Monocytes from these subsets migrate into tissues in response to localized inflammation or injury and provide proinflammatory host defense or antiinflammatory responses and wound healing.

Tissue (organ)-specific macrophages arise from macrophage progenitors that develop in the yolk sac and fetal liver before hematopoiesis occurs in the bone marrow. These cells maintain their population through self-renewal. Tissue macrophages can also be populated to some extent by circulating monocytes. Monocytes or macrophages at sites of active inflammation mature into proinflammatory (M1) macrophages or proresolving (M2) macrophages. In ongoing tissue injury or inflammation, many (perhaps most) of the macrophages will express a mix of the properties of the classic types.

Whether embryonic or blood derived, tissue macrophages are directed by organ-specific factors to differentiate into macrophages characteristic of that organ. Embryonic progenitors or monocytes in the liver become Kupffer cells that bridge the sinusoids separating adjacent plates of hepatocytes. Those at the lung airway surface become large ellipsoid alveolar macrophages , those in the bone become osteoclasts , and those in brain or retina become microglia . All macrophages, however, have at least 3 major functions in common: phagocytosis, presentation of antigens to lymphocytes, and enhancement or suppression of the immune response through release of a variety of potent cytokines. At sites of inflammation, monocytes and macrophages can fuse to form multinucleated giant cells ; these cells maintain the antimicrobial functions of macrophages.