VITAMIN-E INDUCES RAMIFICATION AND DOWN-REGULATION OF ADHESION MOLECULES IN CULTURED MICROGLIAL CELLS

Microglial cells in the healthy adult CNS possess a characteristic ram ified morphology and show little or no expression of major histocompat ibility complex (MHC) or adhesion molecules. In contrast, microglial c ells isolated from newborn rat brains inevitably show a nonramified am oeboid morphology and express immunoeffector molecules, such as MHC cl ass I and II, and various adhesion molecules thought to be markers of microglial activation. Furthermore, they produce large amounts of oxyg en radicals. Treatment of cultured microglial cells with the antioxida nts vitamin E (alpha-tocopherol) and vitamin C (ascorbic acid) induced a ramified microglial morphology after 48 h in vitro, otherwise only seen in healthy adult CNS tissue or in co-culture with astrocytes. Mor phological transformation of microglial cells was quantified by morpho metric analysis and was found to be statistically significant. Ramific ation of microglia induced by vitamin E was accompanied by downregulat ed expression of adhesion molecules leukocyte function antigen-1, very late antigen-4, and intercellular adhesion molecule-1, as assessed by FAGS analysis and immunocytochemistry. Moreover, cell numbers of micr oglia treated with vitamin E remained stable within 7 days in vitro, w hereas untreated controls showed a cell loss of 81.5%. These data show that vitamin E acts as a protective compound in dissociated microglia l cell cultures. In conclusion, our results suggest that vitamin E and vitamin C shift microglial morphology toward ramification and induce an immunological deactivation. These changes seem to be mediated by ox idative mechanisms. (C) 1998 Wiley-Liss, Inc.