Vitamin E induces ramification and downregulation of adhesion molecules in cultured microglial cells.
Microglial cells in the healthy adult CNS possess a characteristic ramified morphology and show little or no expression of major histocompatibility complex (MHC) or adhesion molecules. In contrast, microglial cells isolated from newborn rat brains inevitably show a nonramified amoeboid morphology and express immunoeffector molecules, such as MHC class I and II, and various adhesion molecules thought to be markers of microglial activation. Furthermore, they produce large amounts of oxygen radicals. Treatment of cultured microglial cells with the antioxidants 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. Morphological transformation of microglial cells was quantified by morphometric analysis and was found to be statistically significant. Ramification of microglia induced by vitamin E was accompanied by downregulated expression of adhesion molecules leukocyte function antigen-1, very late antigen-4, and intercellular adhesion molecule-1, as assessed by FACS analysis and immunocytochemistry. Moreover, cell numbers of microglia treated with vitamin E remained stable within 7 days in vitro, whereas untreated controls showed a cell loss of 81.5%. These data show that vitamin E acts as a protective compound in dissociated microglial 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 oxidative mechanisms.
Heppner
F L
FL
Department of Cell and Neurobiology, Institute of Anatomy, Humboldt University Hospital, Berlin, Germany. frank.heppner@rz.hu-berlin.de
Roth
K
K
Nitsch
R
R
Hailer
N P
NP
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E; D001205:Ascorbic Acid