| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Release from Microglia1
* Consiglio Nazionale delle Ricerche-Institute of Neuroscience, Cellular and Molecular Pharmacology and Department of Medical Pharmacology, University of Milan and Center of Excellence on Neurodegenerative Diseases, Milan, Italy; and Department Of Neurology, University of Washington, Seattle, WA 98195
ATP has been indicated as a primary factor in microglial response to brain injury and inflammation. By acting on different purinergic receptors 2, ATP is known to induce chemotaxis and stimulate the release of several cytokines from these cells. The activation of purinergic receptors 2 in microglia can be triggered either by ATP deriving from dying cells, at sites of brain injury or by ATP released from astrocytes, in the absence of cell damage. By the use of a biochemical approach integrated with video microscopy experiments, we investigated the functional consequences triggered in microglia by ATP released from mechanically stimulated astrocytes, in mixed glial cocultures. Astrocyte-derived ATP induced in nearby microglia the formation and the shedding of membrane vesicles. Vesicle formation was inhibited by the ATP-degrading enzyme apyrase or by P2X7R antagonists. Isolation of shed vesicles, followed by IL-1
evaluation by a specific ELISA revealed the presence of the cytokine inside the vesicular organelles and its subsequent efflux into the extracellular medium. IL-1 efflux from shed vesicles was enhanced by ATP stimulation and inhibited by pretreatment with the P2X7 antagonist oxidized ATP, thus indicating a crucial involvement of the pore-forming P2X7R in the release of the cytokine. Our data identify astrocyte-derived ATP as the endogenous factor responsible for microvesicle shedding in microglia and reveal the mechanisms by which astrocyte-derived ATP triggers IL-1 release from these cells.
This article has been cited by other articles:
|
|
 |
|
  Y. Qu, L. Ramachandra, S. Mohr, L. Franchi, C. V. Harding, G. Nunez, and G. R. Dubyak P2X7 Receptor-Stimulated Secretion of MHC Class II-Containing Exosomes Requires the ASC/NLRP3 Inflammasome but Is Independent of Caspase-1 J. Immunol., April 15, 2009; 182(8): 5052 - 5062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Dubyak Both sides now: multiple interactions of ATP with pannexin-1 hemichannels. Focus on "A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP" Am J Physiol Cell Physiol, February 1, 2009; 296(2): C235 - C241. [Full Text] [PDF]
|
|
|
|
|
|
T. Takenouchi, Y. Iwamaru, S. Sugama, M. Sato, M. Hashimoto, and H. Kitani Lysophospholipids and ATP Mutually Suppress Maturation and Release of IL-1{beta} in Mouse Microglial Cells Using a Rho-Dependent Pathway J. Immunol., June 15, 2008; 180(12): 7827 - 7839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pelegrin, C. Barroso-Gutierrez, and A. Surprenant P2X7 Receptor Differentially Couples to Distinct Release Pathways for IL-1{beta} in Mouse Macrophage J. Immunol., June 1, 2008; 180(11): 7147 - 7157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Qu, L. Franchi, G. Nunez, and G. R. Dubyak Nonclassical IL-1beta Secretion Stimulated by P2X7 Receptors Is Dependent on Inflammasome Activation and Correlated with Exosome Release in Murine Macrophages J. Immunol., August 1, 2007; 179(3): 1913 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Baroni, C. Pizzirani, M. Pinotti, D. Ferrari, E. Adinolfi, S. Calzavarini, P. Caruso, F. Bernardi, and F. Di Virgilio Stimulation of P2 (P2X7) receptors in human dendritic cells induces the release of tissue factor-bearing microparticles FASEB J, June 1, 2007; 21(8): 1926 - 1933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Pizzirani, D. Ferrari, P. Chiozzi, E. Adinolfi, D. Sandona, E. Savaglio, and F. Di Virgilio Stimulation of P2 receptors causes release of IL-1{beta}-loaded microvesicles from human dendritic cells Blood, May 1, 2007; 109(9): 3856 - 3864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Stock, T. Schilling, A. Schwab, and C. Eder Lysophosphatidylcholine Stimulates IL-1beta Release from Microglia via a P2X7 Receptor-Independent Mechanism J. Immunol., December 15, 2006; 177(12): 8560 - 8568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Carta, S. Tassi, C. Semino, G. Fossati, P. Mascagni, C. A. Dinarello, and A. Rubartelli Histone deacetylase inhibitors prevent exocytosis of interleukin-1beta-containing secretory lysosomes: role of microtubules Blood, September 1, 2006; 108(5): 1618 - 1626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ferrari, C. Pizzirani, E. Adinolfi, R. M. Lemoli, A. Curti, M. Idzko, E. Panther, and F. Di Virgilio The P2X7 Receptor: A Key Player in IL-1 Processing and Release J. Immunol., April 1, 2006; 176(7): 3877 - 3883. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
