Natural and induced cytotoxicity of oligodendrocytes by microglia is inhibitable by TGF beta.
Blood macrophages and brain macrophages (microglia) have been implicated in demyelination and destruction of the oligodendrocyte in multiple sclerosis (MS), a disease affecting primarily white matter of the central nervous system (CNS). In this study, we demonstrate that at high effector to target cell ratios, normal rat microglia exhibit a natural cytotoxicity against normal rat oligodendrocytes in vitro. The killing is not mediated by the release of soluble factors. The cytotoxic activity is upregulated by pretreatment of microglia with interferon gamma (IFN gamma) or phorbol myristate acetate (PMA). Both the natural and induced cytotoxicities are inhibitable by transforming growth factor beta (TGF beta). The increase in numbers and apposition of primed or activated microglia to oligodendrocytes in MS lesions may give rise to natural or induced killing from which oligodendrocytes may be protected by TGF beta.
Merrill
J E
JE
Department of Neurology, Reed Neurological Research Center, UCLA School of Medicine 90024.
Zimmerman
R P
RP
D000818:Animals; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003864:Depression, Chemical; D005609:Free Radicals; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009103:Multiple Sclerosis / Q000473:pathology; D009836:Oligodendroglia; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005609:Free Radicals; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate