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The role of macrophages in models of neurological and psychiatric disorder

We consider here some of the recent advances in knowledge about the possible functions of the macrophage in the normal and diseased or damaged nervous system. The macrophage forms the key element in interactions between the nervous system and the immune system. Macrophages have a truly remarkable life history. They are generated in the bone marrow, circulate in the blood as monocytes for a day or so and then take up residence in almost all tissues of the body, where they may reside for long periods, sometimes for many years. Tissue macrophages are highly specialized cells showing considerable heterogeneity from tissue to tissue. They play a role in tissue homeostasis but, possibly more importantly, they provide the first line of defence against injury and infection (Gordon, 1986). Tissue macrophages have only a limited capacity for proliferation, but their numbers may be rapidly augmented by recruitment of cells from the blood. These inflammatory or exudate macrophages have the potential to secrete a veritable catalogue of products, some of which are critical for tissue repair and others which may cause autologous tissue damage (Nathan, 1987). Microglia were first described in the central nervous system (CNS) by Rio Hortega (1932), and from that time until the early 1980s a controversy continued as to whether these cells were bloodderived cells or a type of neuroglia (see Ling, 1981 for review). In the last decade overwhelming evidence has accumulated that microglia are indeed the resident macrophages of the CNS (reviewed in Perry & Gordon, 1991). In radiation chimeras cells bearing markers of donor leucocytes have been shown to enter the brain and adopt the form of microglia (Hickey & Kimura, 1988). In the developing nervous system of rodents it has been shown, using antibodies to a macrophage-specific antigen, that monocytes enter the brain and pass through a series of morphological transitions to become microglia (Perry et al. 1985). With improvements in reagents and immunocytochemical methods there is now a long list of cell-surface and cytoplasmic antigens associated with microglia that are found on other leucocytes or restricted to macrophages (Streit et al. 1988; Perry & Gordon, 1991). In addition to microglia within the parenchyma of the brain there are other specialized populations of macrophages associated with the microvasculature (Graeber et al. 1989), the choroid plexus and leptomeninges (Perry et al. 1985).