Activation of purinergic receptors on glial cells is associated with functional responses under normal and pathophysiological conditions. Modulation of purinergic receptors in neurodegenerative and neuroprotective processes have become important therapeutic targets in inflammation and immune-related diseases. Chronic alcohol use causes structural and functional abnormalities of the brain and has a profound impact on the neuroimmune system. As immune effectors in the central nervous system (CNS), microglia are activated in pathological conditions and alcohol induces inflammatory processes in the brain leading to neurodegeneration. Among the P2XR subtypes, P2X4R is copious in the CNS and data suggests them to be important mediators of alcohol-induced effect. Our previous unpublished studies have shown that alcohol significantly increases microglia P2X4 mRNA and protein expression. In this study, we investigated the consequences of P2X4R expression on microglia immune function. Fractalkine induced microglia migration was decreased by 75% following 48hrs of alcohol treatment compared to control (p<0.001), which was attenuated 2.3 fold by pretreatment with 5-BDBD, a P2X4 antagonist. Similarly, 48hrs of alcohol treatment decreased phagocytosis by 15% compared to control (p<0.05), this was significantly reversed when pre-treated with 5-BDBD (p<0.001). Our findings suggest that P2X4 receptors play a role in mediating alcohol-induced effects on microglia immune effector functions.
- Copyright © 2013 by The American Association of Immunologists, Inc.