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

Published online before print February 23, 2005

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.1004597v1 77/6/958    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sylte, M. J. Articles by Czuprynski, C. J. Search for Related Content PubMed PubMed Citation Articles by Sylte, M. J. Articles by Czuprynski, C. J.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1004597

Received for publication October 19, 2004.
Revised January 7, 2005.
Accepted for publication January 25, 2005.

Article

Stimulation of P2X receptors enhances lipooligosaccharide-mediated apoptosis of endothelial cells

Matt J. Sylte ^*, Chris J. Kuckleburg ^*, Thomas J. Inzana , Paul J. Bertics , and Charles J. Czuprynski ^*@

*Department of Pathobiological Sciences, School of Veterinary Medicine, and Department of Biomolecular Chemistry, School of Medicine, University of Wisconsin, Madison; and Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg

^@ To whom correspondence should be addressed. E-mail: czuprync{at}svm.vetmed.wisc.edu.

	Abstract

Exposure of endothelial cells to lipid A-containing molecules, such as lipopolysaccharide (LPS) or lipooligosaccharide (LOS), causes the release of purinergic compounds [e.g., adenosine 5`-triphosphate (ATP)] and can lead to apoptosis. The P2X family of purinergic receptors (e.g., P2X<sub>7</sub>) has been reported to modulate LPS signaling events and to participate in apoptosis. We investigated the role that P2X receptors play in the apoptosis that follows exposure of bovine endothelial cells to Haemophilus somnus LOS. Addition of P2X inhibitors, such as periodate-oxidized ATP (oATP) or pyridoxal-phosphate-6-azophenyl-2`,4`-disulfonic acid tetrasodium, significantly reduced LOS-induced apoptosis. Incubation of endothelial cells with apyrase, which degrades ATP, diminished LOS-induced apoptosis of endothelial cells. Concomitant addition of P2X agonists [e.g., 2`,3`-(4-benzoyl)-benzoyl ATP or ATP] to LOS-treated endothelial cells significantly enhanced caspase-3 activation. The P2X antagonist oATP significantly blocked caspase-8 but not caspase-9 activation in LOS-treated endothelial cells. Together, these data indicate that stimulation of P2X receptors, perhaps P2X₇, enhances LOS-induced apoptosis of endothelial cells, possibly as a result of endogenous release of ATP, which results in caspase-8 activation.

Key Words: purinergic receptor • ATP

This article has been cited by other articles:

				D. McClenahan, K. Hellenbrand, D. Atapattu, N. Aulik, D. Carlton, A. Kapur, and C. Czuprynski Effects of Lipopolysaccharide and Mannheimia haemolytica Leukotoxin on Bovine Lung Microvascular Endothelial Cells and Alveolar Epithelial Cells Clin. Vaccine Immunol., February 1, 2008; 15(2): 338 - 347. [Abstract] [Full Text] [PDF]

				I. Sandal, W. Hong, W. E. Swords, and T. J. Inzana Characterization and Comparison of Biofilm Development by Pathogenic and Commensal Isolates of Histophilus somni J. Bacteriol., November 15, 2007; 189(22): 8179 - 8185. [Abstract] [Full Text] [PDF]

				A. Solini, E. Santini, D. Chimenti, P. Chiozzi, F. Pratesi, S. Cuccato, S. Falzoni, R. Lupi, E. Ferrannini, G. Pugliese, et al. Multiple P2X receptors are involved in the modulation of apoptosis in human mesangial cells: evidence for a role of P2X4 Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1537 - F1547. [Abstract] [Full Text] [PDF]