Microglial cells express a peculiar plasma membrane receptor for extracellular ATP, named P2Z/P2X7 purinergic receptor, that triggers massive transmembrane ion fluxes and a reversible permeabilization of the plasma membrane to hydrophylic molecules of up to 900 dalton molecule weight and eventual cell death (Di Virgilio, F. 1995. Immunol. Today. 16:524–528). The physiological role of this newly cloned (Surprenant, A., F. Rassendren, E. Kawashima, R.A. North and G. Buell. 1996. Science (Wash. DC). 272:735–737) cytolytic receptor is unknown. In vitro and in vivo activation of the macrophage and microglial cell P2Z/P2X7 receptor by exogenous ATP causes a large and rapid release of mature IL-1β. In the present report we investigated the role of microglial P2Z/P2X7 receptor in IL-1β release triggered by LPS. Our data suggest that LPS-dependent IL-1β release involves activation of this purinergic receptor as it is inhibited by the selective P2Z/P2X7 blocker oxidized ATP and modulated by ATP-hydrolyzing enzymes such as apyrase or hexokinase. Furthermore, microglial cells release ATP when stimulated with LPS. LPS-dependent release of ATP is also observed in monocyte-derived human macrophages. It is suggested that bacterial endotoxin activates an autocrine/paracrine loop that drives ATP-dependent IL-1β secretion.
Purinergic Modulation of Interleukin-1β Release from Microglial Cells Stimulated with Bacterial Endotoxin
Address correspondence to Francesco Di Virgilio, Institute of General Pathology, University of Ferrara, Via Borsari, 46, I-44100 Ferrara, Italy.
This work was supported by grants from the National Research Council of Italy (target project Clinical Application of Cancer Research, ACRO), the Ministry of Scientific Research (MURST), the Italian Association for Cancer Research (AIRC), the VIII AIDS Project, the I Tuberculosis Project, and Telethon of Italy.
Davide Ferrari, Paola Chiozzi, Simonetta Falzoni, Stefania Hanau, Francesco Di Virgilio; Purinergic Modulation of Interleukin-1β Release from Microglial Cells Stimulated with Bacterial Endotoxin. J Exp Med 3 February 1997; 185 (3): 579–582. doi: https://doi.org/10.1084/jem.185.3.579
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