| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* School of Pharmaceutical Sciences, University of Shizuoka, and
Center of Excellence Program in the 21st Century, University of Shizuoka, Shizuoka, Japan
Extracellular ATP causes apoptosis and/or necrosis of the hemopoietic lineage through the activation of P2X7 receptors. In this study, we investigated P2X7 receptor-mediated cell death during murine T cell maturation. The expression level and activity of P2X7 receptors, as measured by induction of cell death and pore formation, were higher in splenocytes than thymocytes. Flow cytometric analysis revealed that cell shrinkage was induced by activation of the P2X7 receptor in murine lymphocytes and the responding cells were T cells. Splenic T cells were more responsive than their thymic counterpart. These observations indicate that the system of P2X7 receptor-mediated cell death in T cells could be modulated during T cell maturation. Furthermore, decreased extracellular Cl– suppressed ATP-induced cell shrinkage in splenocytes without inhibiting ERK1/2 phosphorylation, which is reported to mediate necrotic cell death. Treatment with U0126 (a MEK inhibitor) suppressed ATP-induced ERK1/2 phosphorylation without inhibiting cell shrinkage. Moreover, decreased extracellular Cl– and treatment with U0126 suppressed ATP-induced cell death. These observations indicate that the activation of P2X7 receptor leads to T cell death by two independent pathways, one of which is cell shrinkage dependent and the other of which involves the phosphorylation of ERK1/2. In conclusion, we demonstrate increasing P2X7 receptor activity during T cell maturation and the existence of two essential pathways in P2X7 receptor-mediated T cell death. Our findings suggest that ATP-induced cell death of peripheral T lymphocytes is important in P2X7 receptor-regulated immune responses.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants-in-aid from the Ministry of Education, Science, Culture, and Sports of Japan. H.H. received support from Asai Germanium Research Institute.
2 Address correspondence and reprint requests to Dr. Hitoshi Harada, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. E-mail address: harada{at}u-shizuoka-ken.ac.jp
3 Abbreviations used in this paper: BzATP, 2',3'-O-(4-benzoyl)benzoyl-ATP; oATP, oxidized ATP; HMGB1, high mobility group box 1; LDH, lactate dehydrogenase; EtBr, ethidium bromide; PI, propidium iodide.
This article has been cited by other articles:
|
|
 |
|
  P. Worsdorfer, S. Maxeiner, C. Markopoulos, G. Kirfel, V. Wulf, T. Auth, S. Urschel, J. von Maltzahn, and K. Willecke Connexin Expression and Functional Analysis of Gap Junctional Communication in Mouse Embryonic Stem Cells Stem Cells, February 1, 2008; 26(2): 431 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. J. Taylor, M. Gonzalez-Begne, S. Dewhurst, G. Chimini, C. F. Higgins, J. E. Melvin, and J. I. Elliott Sequential Shrinkage and Swelling Underlie P2X7-Stimulated Lymphocyte Phosphatidylserine Exposure and Death J. Immunol., January 1, 2008; 180(1): 300 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-R. Woo, R. G. Barletta, and C. J. Czuprynski Extracellular ATP Is Cytotoxic to Mononuclear Phagocytes but Does Not Induce Killing of Intracellular Mycobacterium avium subsp. paratuberculosis Clin. Vaccine Immunol., September 1, 2007; 14(9): 1078 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. J. Taylor, D. R. Alexander, J. C. Cooper, C. F. Higgins, and J. I. Elliott Regulatory T Cells Are Resistant to Apoptosis via TCR but Not P2X7 J. Immunol., March 15, 2007; 178(6): 3474 - 3482. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
