The role of P2X7 receptor in glial cells

Summary of thesis The aim of this study was to study the functional consequences of the ATP mediated communication between astrocytes and microglia, with particular emphasis on the functional consequences related to the activation of purinergic receptor P2X7 on microglial cells. The results obtained indicate that: 1. that the LPS-induced reduction of functional P2X7 receptor in embryonic microglia may mediate the cell cycle modifications observed upon exposure to the endotoxin. 2. the release of at least a fraction of IL 1-beta from microglia takes place, upon ATP stimulation, through the shedding of vesicles from the plasmamembrane. Shed vesicles appear to be the site of IL 1-beta processing. 3. that intercellular calcium mediated signalling might contribute in cortex more than in the hippocampus to the propagation and maintenance of an inflammatory state. Most importantly, the present study represents the first evidence of microvesicle shedding in the CNS. Just like their systemic counterpart (monocytes) microglial cells are able to form vesicle and release them in a calcium-dependent manner. We have demonstrated that vesicle contain protein elements and that biological processes such as IL 1-beta maturation can occur inside isolated vesicles