Cultured astrocytes express regional heterogeneity of the immunoreactive phenotype under basal conditions and after γ-IFN induction

Abstract

Cerebral astrocytes are known to show a region-specific phenotype, concerning the expression of several receptors and the synthesis of secreted substances. In order to find out whether this heterogeneity also exists for the immunological activation, we studied several parameters that are known to characterize activated astroglia on cultured primary rat astrocytes originating from cortex, hippocampus, striatum, septum and brain stem: major histocompatibility complex (MHC) class II and intercellular adhesion molecule (ICAM)-1 expression, nitric oxide (NO) production and interleukin-6 (IL-6) synthesis. Unstimulated cultures show a baseline expression of MHC class II molecules that differs from one region to another, hippocampus and brain stem showing the highest values. These differences are strongly enhanced after a 48-h incubation with gamma-interferon (gamma-IFN). NO production is also induced by a 72-h incubation with gamma-IFN, showing similar patterns of regional specialization. The baseline expressions of ICAM-1 and IL-6 also show major regional differences, with the brain stem and the striatum showing elevated values for ICAM-1, and the septum and the brain stem producing the largest amounts of IL-6. The expressions of ICAM-1 and IL-6 are not affected by an incubation with gamma-IFN. Our results demonstrate that the immunological activities of astroglial cells show regional heterogeneities. This specialization may be implicated in the pathophysiological pathways of several neurodegenerative disorders.