Purinergic Modulation of Interleukin-1β Release from Microglial Cells Stimulated with Bacterial Endotoxin

Author:

Ferrari Davide1,Chiozzi Paola1,Falzoni Simonetta1,Hanau Stefania1,Di  Virgilio Francesco11

Affiliation:

1. From the Institute of General Pathology, Center of Biotechnology, Department of Biochemistry and Molecular Biology, University of Ferrara, I-44100 Ferrara Italy

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Reference20 articles.

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3. Signalling via ATP in the nervous system;Zimmermann;Trends Neurosci,1994

4. Potassium-inhibited processing of IL-1β in human monocytes;Walev;EMBO (Eur Mol Biol Organ) J,1995

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