HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beigi, R. D. Articles by Dubyak, G. R. Search for Related Content PubMed PubMed Citation Articles by Beigi, R. D. Articles by Dubyak, G. R.

Endotoxin Activation of Macrophages Does Not Induce ATP Release and Autocrine Stimulation of P2 Nucleotide Receptors¹

Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106

Receptors for extracellular nucleotides (P2, or purinergic receptors) have previously been implicated in the transduction of endotoxin signaling in macrophages. The most compelling evidence has been the observation that inhibitors of ionotropic nucleotide (P2X) receptors, including periodate-oxidized ATP (oATP), attenuate a subset of endotoxin-induced effects such as activation of NF-B and up-regulation of inducible NO synthase. We investigated whether endotoxin induces ATP release from a murine macrophage cell line (BAC1.2F5) using sensitive on-line assays for extracellular ATP. These cells constitutively released ATP, producing steady-state extracellular concentrations of 1 nM when assayed as monolayers of 10⁶ adherent cells bathed in 1 ml of medium. However, the macrophages did not release additional ATP during either acute or prolonged endotoxin stimulation. In addition, cellular ecto-ATPase activities were measured following prolonged endotoxin activation and were found not to be significantly altered. Although oATP treatment significantly attenuated the endotoxin-induced production of NO, this inhibitory effect was not reproduced when the cells were coincubated with apyrase, a highly effective ATP scavenger. These results indicate that activation of macrophages by endotoxin does not induce autocrine stimulation of P2 nucleotide receptors by endogenous ATP released to extracellular compartments. Moreover, the data suggest that the ability of oATP to interfere with endotoxin signaling is due to its interaction with molecular species other than ATP-binding P2 receptors.

This article has been cited by other articles:

				M. S. Bentle, K. E. Reinicke, E. A. Bey, D. R. Spitz, and D. A. Boothman Calcium-dependent Modulation of Poly(ADP-ribose) Polymerase-1 Alters Cellular Metabolism and DNA Repair J. Biol. Chem., November 3, 2006; 281(44): 33684 - 33696. [Abstract] [Full Text] [PDF]

				M. P. Abbracchio, G. Burnstock, J.-M. Boeynaems, E. A. Barnard, J. L. Boyer, C. Kennedy, G. E. Knight, M. Fumagalli, C. Gachet, K. A. Jacobson, et al. International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy Pharmacol. Rev., September 1, 2006; 58(3): 281 - 341. [Abstract] [Full Text] [PDF]

				J. M. Kahlenberg, K. C. Lundberg, S. B. Kertesy, Y. Qu, and G. R. Dubyak Potentiation of Caspase-1 Activation by the P2X7 Receptor Is Dependent on TLR Signals and Requires NF-{kappa}B-Driven Protein Synthesis J. Immunol., December 1, 2005; 175(11): 7611 - 7622. [Abstract] [Full Text] [PDF]

				S. Chivasa, B. K. Ndimba, W. J. Simon, K. Lindsey, and A. R. Slabas Extracellular ATP Functions as an Endogenous External Metabolite Regulating Plant Cell Viability PLANT CELL, November 1, 2005; 17(11): 3019 - 3034. [Abstract] [Full Text] [PDF]

				L. C. Denlinger, G. Angelini, K. Schell, D. N. Green, A. G. Guadarrama, U. Prabhu, D. B. Coursin, P. J. Bertics, and K. Hogan Detection of Human P2X7 Nucleotide Receptor Polymorphisms by a Novel Monocyte Pore Assay Predictive of Alterations in Lipopolysaccharide-Induced Cytokine Production J. Immunol., April 1, 2005; 174(7): 4424 - 4431. [Abstract] [Full Text] [PDF]

				B. J. Johnson, T. T. T. Le, C. A. Dobbin, T. Banovic, C. B. Howard, F. d. M. L. Flores, D. Vanags, D. J. Naylor, G. R. Hill, and A. Suhrbier Heat Shock Protein 10 Inhibits Lipopolysaccharide-induced Inflammatory Mediator Production J. Biol. Chem., February 11, 2005; 280(6): 4037 - 4047. [Abstract] [Full Text] [PDF]

				F. S. A. Fortes, I. L. Pecora, P. M. Persechini, S. Hurtado, V. Costa, R. Coutinho-Silva, M. B. M. Braga, F. C. Silva-Filho, R. C. Bisaggio, F. P. de Farias, et al. Modulation of intercellular communication in macrophages: possible interactions between GAP junctions and P2 receptors J. Cell Sci., September 15, 2004; 117(20): 4717 - 4726. [Abstract] [Full Text] [PDF]

				E. R. Lazarowski, R. C. Boucher, and T. K. Harden Mechanisms of Release of Nucleotides and Integration of Their Action as P2X- and P2Y-Receptor Activating Molecules Mol. Pharmacol., October 1, 2003; 64(4): 785 - 795. [Full Text] [PDF]

				S. M. Joseph, M. R. Buchakjian, and G. R. Dubyak Colocalization of ATP Release Sites and Ecto-ATPase Activity at the Extracellular Surface of Human Astrocytes J. Biol. Chem., June 20, 2003; 278(26): 23331 - 23342. [Abstract] [Full Text] [PDF]

				D. H. Canaday, R. Beigi, R. F. Silver, C. V. Harding, W. H. Boom, and G. R. Dubyak ATP and Control of Intracellular Growth of Mycobacteria by T Cells Infect. Immun., November 1, 2002; 70(11): 6456 - 6459. [Abstract] [Full Text] [PDF]

				M. Idzko, S. Dichmann, D. Ferrari, F. Di Virgilio, A. la Sala, G. Girolomoni, E. Panther, and J. Norgauer Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors Blood, July 18, 2002; 100(3): 925 - 932. [Abstract] [Full Text] [PDF]

				T. Into, M. Fujita, T. Okusawa, A. Hasebe, M. Morita, and K.-I. Shibata Synergic Effects of Mycoplasmal Lipopeptides and Extracellular ATP on Activation of Macrophages Infect. Immun., July 1, 2002; 70(7): 3586 - 3591. [Abstract] [Full Text] [PDF]

				G. R. Dubyak Focus on "Extracellular ATP signaling and P2X nucleotide receptors in monolayers of primary human vascular endothelial cells" Am J Physiol Cell Physiol, February 1, 2002; 282(2): C242 - C244. [Full Text] [PDF]

				R. A. Le Feuvre, D. Brough, Y. Iwakura, K. Takeda, and N. J. Rothwell Priming of Macrophages with Lipopolysaccharide Potentiates P2X7-mediated Cell Death via a Caspase-1-dependent Mechanism, Independently of Cytokine Production J. Biol. Chem., January 25, 2002; 277(5): 3210 - 3218. [Abstract] [Full Text] [PDF]

				W. Panenka, H. Jijon, L. M. Herx, J. N. Armstrong, D. Feighan, T. Wei, V. W. Yong, R. M. Ransohoff, and B. A. MacVicar P2X7-Like Receptor Activation in Astrocytes Increases Chemokine Monocyte Chemoattractant Protein-1 Expression via Mitogen-Activated Protein Kinase J. Neurosci., September 15, 2001; 21(18): 7135 - 7142. [Abstract] [Full Text] [PDF]

				C. Tagliarino, J. J. Pink, G. R. Dubyak, A.-L. Nieminen, and D. A. Boothman Calcium Is a Key Signaling Molecule in beta -Lapachone-mediated Cell Death J. Biol. Chem., May 25, 2001; 276(22): 19150 - 19159. [Abstract] [Full Text] [PDF]

				M. Warny, S. Aboudola, S. C. Robson, J. Sevigny, D. Communi, S. P. Soltoff, and C. P. Kelly P2Y6 Nucleotide Receptor Mediates Monocyte Interleukin-8 Production in Response to UDP or Lipopolysaccharide J. Biol. Chem., July 6, 2001; 276(28): 26051 - 26056. [Abstract] [Full Text] [PDF]