Microglia: immunoregulatory cells in the central nervous system.

Microglia are one of three types of glial cells in the central nervous system (CNS). Although the origin of the cells is still controversial, several lines of evidences suggest that they are bone marrow-derived, monocyte-macrophage lineage cells that enter the brain during embryonic development and differentiate into ramified resting microglia through a series of morphologic transformations. After the development of isolation and culture techniques for microglia, many reports have indicated their morphological and functional similarities to monocyte-macrophages. They have complement receptors recognized with Mac 1 or OX42 monoclonal antibody, Fc receptors (Suzumura et al., 1987), CD4 (Sawada et al., 1992b) and CD14 antigens on their surface (unpublished observation), and react with the antibodies against surface molecules of macrophages such as F4/80, ED1, ED2, and EMB11(Austin et al., 1981, Perry et al., 1985, Dijkstra et al., 1985, Imamura et al., 1990). Microglia are also identified by binding with lectins, such as RCA-1 lectin and GSA-1 lectin (Mannoji et al., 1986, Streit et al., 1987). They express class I major histocompatibility complex (MHC) antigens and are induced to express class II MHC antigens (Suzumura et al., 1987). Microglia phagocytose letex beads in vitro and are considered to remove remnants as phogocytic cells during the neurogenesis. Furthermore, they are regulated in growth, differentiation and activation by the same cytokines as are monocyte-macrophages (Sawada et al., 1990, 1999, Suzumura et al., 1990, 1991, 1998), and produce the same monokines, such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor (TNF)α as macrophages do (Giulian et al., 1986, Heiter et al., 1988, Frei et al., 1989, Sawada et al., 1989, 1992a, Tomozawa et al., 1995). They also produce IL-12 (Suzumura et al. 1998) and IL18 (Suzumura et al. 2001), the cytokines which regulate differentiation of T helper cells, and several chemokines. Therefore, microglia are considered to play similar roles as macrophages in the CNS, functioning as scavenger cells, inflammatory cells, antigen-presenting cells, and immunoregulatory cells. In addition, microglia may function as effector cells that induce demyelination or neuronal degeneration, and may also play a major part in the development of gliosis via secreting cytokines or some other soluble factors (Giulian et al., 1985, Selmaj et al., 1990, Suzumura et al., 1993a). In this review, we focused on the immunoregulatory functions, including antigen presentation and cytokine production, of microglia in physiological and pathological conditions in the CNS.