Chapter 4.3 - Chemokine Interactions with Astrocytes

Abstract

This chapter summarizes the effects of chemokines on astrocytes and the potential receptors responsible for these interactions. Chemokines stimulate a variety of astrocyte responses in vitro, including cell migration, cytokine and chemokine production, and modulation of heterologous receptors. In vivo evidence supporting each type of response was reported using genetically engineered mouse models in which chemokine expression was targeted to the central nervous system (CNS) or in inflammatory diseases affecting the CNS. Accumulating data suggest several additional chemokine and orphan receptors are also present on astrocytes. The sources and biological function of chemokines along with their cognate receptors on leukocytes are well described. Although there is ample evidence at the RNA and protein level that chemokine receptors are expressed on astrocytes, the functional significance of these astrocyte receptors remains an item of conjecture. Most astrocyte chemokine receptors are expressed in both primates and rodents, but species differences may regulate receptor distribution for some chemokine receptors. The signaling mechanisms responsible for triggering astrocyte responses are under investigation, with preliminary data hinting that distinct signaling pathways may differentially control astrocyte responsiveness. The receptor modulation that accompanies chemokine stimulation further contributes to the dynamic nature of astrocytes.