Astrocytes inhibit microglial surface expression of dendritic cell-related co-stimulatory molecules through a contact-mediated process
Article first published online: 27 MAR 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 125, Issue 4, pages 575–587, May 2013
How to Cite
J. Neurochem.(2013) 125, 575–587.
- Issue published online: 25 APR 2013
- Article first published online: 27 MAR 2013
- Accepted manuscript online: 25 FEB 2013 12:00AM EST
- Manuscript Revised: 8 FEB 2013
- Manuscript Accepted: 8 FEB 2013
- Manuscript Received: 20 JAN 2013
- dendritic cells;
Murine microglia cultured in isolation were treated sequentially with granulocyte/monocyte colony-stimulating factor (GM-CSF) (5 days) and lipopolysaccharide (LPS) (2 days) to elicit a mature dendritic cell-like (DC-like) phenotype. Examined by flow cytometry microglia thus isolated show high surface expression of CD11c together with the co-stimulatory molecules CD40, CD80, and CD86 that are necessary for T-cell activation. In contrast, microglia co-cultured with astrocytes fail to achieve a mature DC-like phenotype. Contact with the astrocytic environment is necessary for the inhibition. Failure was not because of a more rapid degradation of protein. Bone marrow-derived cells, like microglia, were prevented by astrocytes from attaining a mature DC phenotype. Although GM-CSF pre-treatment substantially increases mRNA of co-stimulatory molecules and major histocompatibility complex (MHC) Class II in isolated microglia, co-cultured microglia await treatment with LPS to up-regulate them. In contrast, western blot and immunocytochemical analysis revealed that it is not a failure of transcription or translation, nor is it a more rapid degradation of mRNA that is responsible for the low surface expression; rather microglia co-cultured with astrocytes produce mRNA and protein but do not traffic the protein onto the cell surface.