title: Transient acidification and subsequent proinflammatory cytokine stimulation of astrocytes induce distinct activation phenotypes.
abstract: The foot processes of astrocytes cover over 60% of the surface of brain microvascular endothelial cells, regulating tight junction integrity. Retraction of astrocyte foot processes has been postulated to be a key mechanism in pathology. Therefore, movement of an astrocyte in response to a proinflammatory cytokine or even limited retraction of processes would result in leaky junctions between endothelial cells. Astrocytes lie at the gateway to the CNS and are instrumental in controlling leukocyte entry. Cultured astrocytes typically have a polygonal morphology until stimulated. We hypothesized that cultured astrocytes which were induced to stellate would have an activated phenotype compared with polygonal cells. We investigated the activation of astrocytes derived from adult macaques to the cytokine TNF-α under resting and stellated conditions by four parameters: morphology, intermediate filament expression, adhesion, and cytokine secretion. Astrocytes were stellated following transient acidification; resulting in increased expression of GFAP and vimentin. Stellation was accompanied by decreased adhesion that could be recovered with proinflammatory cytokine treatment. Surprisingly, there was decreased secretion of proinflammatory cytokines by stellated astrocytes compared with polygonal cells. These results suggest that astrocytes are capable of multiple phenotypes depending on the stimulus and the order stimuli are applied.
authors.affiliation: Program in Neuroscience, Tulane University, New Orleans, LA, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Renner
authors.forename: Hope A
authors.initials: HA
authors.lastname: Sansing
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Inglis
authors.forename: Smriti
authors.initials: S
authors.lastname: Mehra
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaushal
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Maclean
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002021:Buffers; D002448:Cell Adhesion; D048430:Cell Shape; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006531:HEPES / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D018836:Inflammation Mediators / Q000378:metabolism*; D007382:Intermediate Filaments / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D010641:Phenotype; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002021:Buffers; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D019006:Neural Cell Adhesion Molecules; D014746:Vimentin; D006531:HEPES