[Frontiers in Bioscience 2, d88-125, March 1, 1997]
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CROSS-TALK SIGNALS IN THE CNS: ROLE OF NEUROTROPHIC AND HORMONAL FACTORS, ADHESION MOLECULES AND INTERCELLULAR SIGNALING AGENTS IN LUTEINIZING HORMONE-RELEASING HORMONE (LHRH)-ASTROGLIAL INTERACTIVE NETWORK

Bianca Marchetti

Department of Pharmacology, Medical School, University of Catania, 95125 Catania, Laboratory of Biotech. Neuropharmacology, OASI Institute for Research and Care (IRCCS) on Mental Retardation and Brain Aging (IRCCS) Troina, (EN), Italy.

Received 8/2/96; Accepted 2/20/97; On-line 3/1/97

6. Immune System Modulation of Neuron-Glia Interactions

6.1. Immunological mediators

One focus of attention in the research on astroglial-neuronal interactions concerns the role of astrocyte-derived immune factors in neuronal pathophysiologylogy. A key compartment is represented by the microglia, which is the resident brain tissue representative of the immune system (32, 33). Astroglia (microglia and astrocytes) in culture can be induced to express major histocompatibility complex (MHC) glycoproteins of class I and II by stimulation with gamma-interferon (tau-IFN), or tumor necrosis factor. They have, then, been proposed as possible antigen-presenting cells, thus influencing immune reactions by their production of various agents that signal the immune system (see 32-38, for reviews). Astrocytes, for example, have been shown to be a major source of clusterin (37). In culture, they can be induced to secrete a variety of cytokines and growth factors including colony stimulating factor 1, which markedly stimulates the proliferation of macrophages (37). The eicosanoids produced by astrocytes may also influence immune regulation. In turn, the interleukin family of growth factors alters powerfully astroglia cell physiology. Interleukin 1 (IL-1) is a potent mitogen for astroglial cells and induces astrocytes to synthesize NGF (124). Interleukin 2 and its receptor occur in the brain and this protein promotes the division and maturation of oligodendrocytes and the survival of peripheral nervous system neurons in culture (125). Interleukin 3 supports the survival of cholinergic neurons in culture and in adult rats with experimental lesions (126). Interleukin 6 promotes survival of cholinergic and dopaminergic neurons developing in culture (127). Finally, tau-IFN stimulates the differentiation of embryonic hippocampal and cortical neurons in culture (128). These findings on interleukins and interferon suggest a close interrelationship between neurotrophic and hemopoietic factors and that mechanisms thought to be specific for the immune system play a role in the CNS (Fig. 7). Recent evidence suggests the participation of the immune system in the communication between the neuronal and astroglial compartments. The activation of astrocytes and microglia may contribute to either the initiation or propagation of intracerebral immune responses (37).

Figure 7. Relationship of brain microglia to other cells of the monocyte phagocytic system. Unifying concept put forward by van Furth (see McGeer and McGeer, 1994), recognizing the relationship between circulating monocytes and tissue histiocytes.

A number of brain injuries have been reported to induce proliferation of reactive microglia, including local injection of a variety of neurotoxic agents (such as kainic acid, 6-hydroxydopamine, 5-6, dihydroxitryptamine).Therefore, the contribution of astroglia in a number of neurochemical effects observed following such lesions, should be reconsidered (see 37 for comprehensive review).