|
|
||||||||



*
Department of Immunology, Holland Lab, American Red Cross, Rockville, MD 20855;
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109
A functional role for stimulated nitric oxide (NO) production was tested in the TCR-triggered death of mature T lymphocytes. In purified peripheral human T cell blasts or the 2B4 murine T cell hybridoma, apoptotic cell death induced by immobilized anti-CD3 was blocked by inhibitors of NO synthase (NOS) in a stereospecific and concentration-dependent manner. This effect appeared to be selective since apoptotic death induced by anti-Fas Ab or the steroid dexamethasone was not affected by NOS inhibitors. TCR-stimulated expression of functional Fas ligand was attenuated in a stereospecific manner by NOS inhibitors, but these compounds did not inhibit TCR-stimulated IL-2 secretion or CD69 surface expression. Nitrosylated tyrosines, a stable marker for NO generation, were immunochemically detected in T cells using flow cytometry. TCR signals induced NO production, as measured by an increase in nitrotyrosine-specific staining. NOS enzymatic activity was detected in lysates of 2B4 cells, and Western blot analysis suggests that the activity is due to expression of the neuronal isoform of NOS. Thus, T cells have the capacity to generate NO upon Ag signaling, which may affect signal transduction, Fas ligand surface expression, and apoptotic cell death of mature T lymphocytes.
This article has been cited by other articles:
![]() |
J. D. Erusalimsky and S. Moncada Nitric Oxide and Mitochondrial Signaling: From Physiology to Pathophysiology Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2524 - 2531. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Haramaki, H. Ikeda, K. Takenaka, A. Katoh, R. Sugano, S.-i. Yamagishi, H. Matsuoka, and T. Imaizumi Fluvastatin Alters Platelet Aggregability in Patients With Hypercholesterolemia: Possible Improvement of Intraplatelet Redox Imbalance via HMG-CoA Reductase Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1471 - 1477. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Morita, H. Ikeda, N. Haramaki, H. Eguchi, and T. Imaizumi Only two-week smoking cessation improves platelet aggregability and intraplatelet redox imbalance of long-term smokers J. Am. Coll. Cardiol., February 15, 2005; 45(4): 589 - 594. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. J. Salmond, R. Williams, T. R. Hirst, and N. A. Williams The B Subunit of Escherichia coli Heat-Labile Enterotoxin Induces Both Caspase-Dependent and -Independent Cell Death Pathways in CD8+ T Cells Infect. Immun., October 1, 2004; 72(10): 5850 - 5857. [Abstract] [Full Text] [PDF] |
||||
![]() |
M.-B. Voisin, D. Buzoni-Gatel, D. Bout, and F. Velge-Roussel Both Expansion of Regulatory GR1+ CD11b+ Myeloid Cells and Anergy of T Lymphocytes Participate in Hyporesponsiveness of the Lung-Associated Immune System during Acute Toxoplasmosis Infect. Immun., September 1, 2004; 72(9): 5487 - 5492. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. L. M. Ricciardolo, P. J. Sterk, B. Gaston, and G. Folkerts Nitric Oxide in Health and Disease of the Respiratory System Physiol Rev, July 1, 2004; 84(3): 731 - 765. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Sharma, S. A.V. Raghavan, R. Saini, and M. Dikshit Ascorbate-mediated enhancement of reactive oxygen species generation from polymorphonuclear leukocytes: modulatory effect of nitric oxide J. Leukoc. Biol., June 1, 2004; 75(6): 1070 - 1078. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Nagy, A. Koncz, and A. Perl T Cell Activation-Induced Mitochondrial Hyperpolarization Is Mediated by Ca2+- and Redox-Dependent Production of Nitric Oxide J. Immunol., November 15, 2003; 171(10): 5188 - 5197. [Abstract] [Full Text] [PDF] |
||||
![]() |
T.-A. Kim, H. K. Avraham, Y.-H. Koh, S. Jiang, I.-W. Park, and S. Avraham HIV-1 Tat-Mediated Apoptosis in Human Brain Microvascular Endothelial Cells J. Immunol., March 1, 2003; 170(5): 2629 - 2637. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Liversidge, A. Dick, and S. Gordon Nitric Oxide Mediates Apoptosis Through Formation of Peroxynitrite and Fas/Fas-Ligand Interactions in Experimental Autoimmune Uveitis Am. J. Pathol., March 1, 2002; 160(3): 905 - 916. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Devadas, L. Zaritskaya, S. G. Rhee, L. Oberley, and M. S. Williams Discrete Generation of Superoxide and Hydrogen Peroxide by T Cell Receptor Stimulation: Selective Regulation of Mitogen-Activated Protein Kinase Activation and Fas Ligand Expression J. Exp. Med., January 7, 2002; 195(1): 59 - 70. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Kanaya, H. Ikeda, N. Haramaki, T. Murohara, and T. Imaizumi Intraplatelet Tetrahydrobiopterin Plays an Important Role in Regulating Canine Coronary Arterial Thrombosis by Modulating Intraplatelet Nitric Oxide and Superoxide Generation Circulation, November 13, 2001; 104(20): 2478 - 2484. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Takajo, H. Ikeda, N. Haramaki, T. Murohara, and T. Imaizumi Augmented oxidative stress of platelets in chronic smokers: Mechanisms of impaired platelet-derived nitric oxide bioactivity and augmented platelet aggregability J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1320 - 1327. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Secchiero, A. Gonelli, C. Celeghini, P. Mirandola, L. Guidotti, G. Visani, S. Capitani, and G. Zauli Activation of the nitric oxide synthase pathway represents a key component of tumor necrosis factor-related apoptosis-inducing ligand-mediated cytotoxicity on hematologic malignancies Blood, October 1, 2001; 98(7): 2220 - 2228. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Jiménez, J. González-Nicolás, S. Alvarez, M. Fresno, and M. A. Muñoz-Fernández Regulation of Human Immunodeficiency Virus Type 1 Replication in Human T Lymphocytes by Nitric Oxide J. Virol., May 15, 2001; 75(10): 4655 - 4663. [Abstract] [Full Text] |
||||
![]() |
R. Roozendaal, E. Vellenga, M. A. de Jong, K. F. Traanberg, D. S. Postma, J. G. R. de Monchy, and H. F. Kauffman Resistance of activated human Th2 cells to NO-induced apoptosis is mediated by {{gamma}}-glutamyltranspeptidase Int. Immunol., April 1, 2001; 13(4): 519 - 528. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. P. Cherla and R. K. Ganju Stromal Cell-Derived Factor 1{{alpha}}-Induced Chemotaxis in T Cells Is Mediated by Nitric Oxide Signaling Pathways J. Immunol., March 1, 2001; 166(5): 3067 - 3074. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. K. Dalton, L. Haynes, C.-Q. Chu, S. L. Swain, and S. Wittmer Interferon {gamma} Eliminates Responding CD4 T Cells during Mycobacterial Infection by Inducing Apoptosis of Activated CD4 T Cells J. Exp. Med., July 3, 2000; 192(1): 117 - 122. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Angulo, F. G. de las Heras, J. F. Garcia-Bustos, D. Gargallo, M. A. Munoz-Fernandez, and M. Fresno Nitric oxide-producing CD11b+Ly-6G(Gr-1)+CD31(ER-MP12)+ cells in the spleen of cyclophosphamide-treated mice: implications for T-cell responses in immunosuppressed mice Blood, January 1, 2000; 95(1): 212 - 220. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Allione, P. Bernabei, M. Bosticardo, S. Ariotti, G. Forni, and F. Novelli Nitric Oxide Suppresses Human T Lymphocyte Proliferation Through IFN-{gamma}-Dependent and IFN-{gamma}-Independent Induction of Apoptosis J. Immunol., October 15, 1999; 163(8): 4182 - 4191. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |