The mononuclear phagocyte system consists of monocytes in the blood, macrophages, and DCs. Monocytes are 10 to 18 μm in diameter, with a single lobed, kidney bean–shaped nucleus. They represent 3% to 8% of peripheral blood leukocytes. Monocytes follow neutrophils into tissue as an early cellular component of inflammation. Monocytes are bone marrow derived and then can differentiate into macrophages and DCs.
Macrophages are long-lived cells that may be resident in tissues and derived from the embryonic yolk sack or fetal liver or derived from monocytes that are recruited to the tissue. They are phagocytic, contain lysosomes and are important for interacting with T cells. Macrophages have the following basic functions: (1) phagocytosis and degradation of debris and microbes, (2) antigen presentation (APC) to T cells to expand specific immune responses, and (3) secretion of cytokines to either maintain normal tissue function and repair (M2 macrophages) or be antimicrobial and pro mote inflammation (M1 macrophages) (Fig. 1). Macrophages express cell-surface receptors for the Fc portion of immunoglobulin (Ig)G (Fc-γ RI, Fc-γ RII, Fc-γ RIII) and for the C3b product of the complement cascade (CR1, CR3). These receptors facilitate the phagocytosis and clearance of antigen, dead cells, bacteria, or viruses coated with these proteins. Toll-like and other pattern-recognition receptors recognize pathogen-associated molecular patterns (PAMP) and activate protective responses. Macrophages also express the class II MHC antigen, which allows these cells to present antigen to CD4 helper T cells to expand the immune response. Macrophages secrete interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, IL 12, IL-23, and other molecules on sensing bacteria, which stimulates innate, immune and inflammatory responses, including fever.
Fig1. Macrophage surface structures mediate multiple cell functions. Receptors for bacterial components, antibody, and complement (for opsonization) promote activation and phagocytosis of antigen; other receptors promote antigen presentation and activation of T cells. The dendritic cell shares many of these characteristics. ICAM-1, Intercellular adhesion molecule-1; IFN-γ, interferon-γ; Ig, immunoglobulin; LFA-3, leukocyte function–associated antigen-3; LPS, lipopolysaccharide; MHC, major histocompatibility antigen I or II; TNF-α, tumor necrosis factor-α.
Tissue resident macrophages include alveolar macro phages in the lungs, Kupffer cells in the liver, intraglomerular mesangial cells in the kidney, histiocytes in connective tis sue, osteoclasts in bone, synovial cells in joints, and microglial cells in the brain. These macrophages are descended from cells of the yolk sac or fetal liver and are primarily involved in tissue maintenance, angiogenesis, and repair functions (like M2 macrophages). The mature forms of these cells have different morphologies corresponding to their ultimate tissue location and function and may express a subset of macrophage activities or cell-surface markers.
Recruited monocytes and macrophages activated by a T cell–derived cytokine, IFN-γ, generate M1 macrophages. These macrophages have enhanced phagocytic, killing, and antigen-presenting capabilities and produce cytokines that promote inflammation.
