Chapter 12 P2Y₆-Evoked Microglial Phagocytosis

While it was reported that microglia is engaged in the clearance of dead cells or dangerous debris, the mechanism of phagocytosis is still unclear. Recently, we found that purinergic system has a very important role for the chemotaxis and phagocytosis of microglia. When neighboring cells are injured, the cells release or leak ATP into extracellular space and microglia rapidly move toward or extend a process to the nucleotides as chemotaxis through P2Y₁₂ receptors of microglia. In the meanwhile, microglia expressing metabotropic P2Y₆ receptors show phagocytosis by the stimulation of uridine 5′-diphosphate (UDP), an agonist of P2Y₆. UDP/UTP is leaked when hippocampal neurons are damaged by kainic acid (KA) in vivo and in vitro. Systemic administration of KA in rats results in neuronal cell death in the hippocampal CA1 and CA3 regions, where mRNA for P2Y₆ receptors increases activated microglia. Thus, the P2Y₆ receptor is upregulated when neurons are damaged, and would function as a sensor for phagocytosis by sensing diffusible UDP signals.