title: Astrocytes inhibit microglial surface expression of dendritic cell-related co-stimulatory molecules through a contact-mediated process.
abstract: 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.
authors: Rutgers University/Newark, Newark, New Jersey, USA.
authors: Giselles
authors: G
authors: Acevedo
authors: Nischal K
authors: NK
authors: Padala
authors: Li
authors: L
authors: Ni
authors: G M
authors: GM
authors: Jonakait
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology* / Q000502:physiology; D018122:B7-1 Antigen / Q000235:genetics* / Q000378:metabolism; D051940:B7-2 Antigen / Q000235:genetics* / Q000378:metabolism; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics* / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology* / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor