Modulation of Microglia by P2X and P2Y Receptors

Microglial cells are involved in a complex series of physiologic and pathophysiologic interactions in the nervous system, and the receptors responsible for mediating these responses are central to coordinating these responses. ATP is a key extracellular signaling molecule in brain and retinal injury, and our previous results indicate release of ATP through pannexin hemichannels following mechanical injury to astrocytes. We ask here whether ATP alters migration, reactivation state and cytokine release in retinal and brain microglial cells. Using a Boyden chamber, ATP was shown to be a powerful chemoattractant for primary microglial cells isolated from both the brain and the retina. Detection of Hoechst-labeled microglia on the lower side of the chamber peaked after 3 hours. Microglial migration was reduced by exposure of the cells to the P2Y12 antagonist ARC-69931, while the P2X7 antagonist A839977 had no effect. Exposure of primed microglia to ATP led to the release of IL-1β. This release was mimicked wit...