The JI PBL Intereron Source
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nakagawa, R.
Right arrow Articles by Seki, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakagawa, R.
Right arrow Articles by Seki, S.
The Journal of Immunology, 2001, 166: 6578-6584.
Copyright © 2001 by The American Association of Immunologists

Mechanisms of the Antimetastatic Effect in the Liver and of the Hepatocyte Injury Induced by {alpha}-Galactosylceramide in Mice

Ryusuke Nakagawa*, Ikuko Nagafune*, Yoshiko Tazunoki*, Hiromi Ehara*, Hitomi Tomura*, Rieko Iijima*, Kazuhiro Motoki*, Masaru Kamishohara* and Shuhji Seki1,{dagger}

* Pharmaceutical Research Laboratory, Kirin Brewery Company, Takasaki, Japan; and {dagger} Division of Basic Traumatology, National Defense Medical College Research Institute, Tokorozawa, Japan

The role of mouse liver NK1.1 Ag+ T (NKT) cells in the antitumor effect of {alpha}-galactosylceramide ({alpha}-GalCer) has been unclear. We now show that, whereas {alpha}-GalCer increased the serum IFN-{gamma} concentration and alanine aminotransferase activity in NK cell-depleted C57BL/6 (B6) mice and B6-beige/beige mice similarly to its effects in control B6 mice, its enhancement of the antitumor cytotoxicity of liver mononuclear cells (MNCs) was abrogated. Depletion of both NK and NKT cells in B6 mice reduced all these effects of {alpha}-GalCer. Injection of Abs to IFN-{gamma} also inhibited the {alpha}-GalCer-induced increase in antitumor cytotoxicity of MNCs. {alpha}-GalCer induced the expression of Fas ligand on NKT cells in the liver of B6 mice. Whereas {alpha}-GalCer did not increase serum alanine aminotransferase activity in B6-lpr/lpr mice and B6-gld/gld mice, it increased the antitumor cytotoxicity of liver MNCs. The {alpha}-GalCer-induced increase in survival rate apparent in B6 mice injected intrasplenically with B16 tumor cells was abrogated in beige/beige mice, NK cell-depleted B6 mice, and B6 mice treated with Abs to IFN-{gamma}. Depletion of CD8+ T cells did not affect the {alpha}-GalCer-induced antitumor cytotoxicity of liver MNCs but reduced the effect of {alpha}-GalCer on the survival of B6 mice. Thus, IFN-{gamma} produced by {alpha}-GalCer-activated NKT cells increases both the innate antitumor cytotoxicity of NK cells and the adaptive antitumor response of CD8+ T cells, with consequent inhibition of tumor metastasis to the liver. Moreover, NKT cells mediate {alpha}-GalCer-induced hepatocyte injury through Fas-Fas ligand signaling.




This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
A. Motegi, M. Kinoshita, A. Inatsu, Y. Habu, D. Saitoh, and S. Seki
IL-15-induced CD8+CD122+ T cells increase antibacterial and anti-tumor immune responses: implications for immune function in aged mice
J. Leukoc. Biol., October 1, 2008; 84(4): 1047 - 1056.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Wang, S. Cho, A. Ueno, L. Cheng, B.-Y. Xu, M. D. Desrosiers, Y. Shi, and Y. Yang
Ligand-Dependent Induction of Noninflammatory Dendritic Cells by Anergic Invariant NKT Cells Minimizes Autoimmune Inflammation
J. Immunol., August 15, 2008; 181(4): 2438 - 2445.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
M. Biburger and G. Tiegs
Activation-induced NKT cell hyporesponsiveness protects from {alpha}-galactosylceramide hepatitis and is independent of active transregulatory factors
J. Leukoc. Biol., July 1, 2008; 84(1): 264 - 279.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. N. Ajuebor
Role of NKT Cells in the Digestive System. I. Invariant NKT cells and liver diseases: is there strength in numbers?
Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G651 - G656.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
R. Safadi, E. Zigmond, O. Pappo, Z. Shalev, and Y. Ilan
Amelioration of hepatic fibrosis via beta-glucosylceramide-mediated immune modulation is associated with altered CD8 and NKT lymphocyte distribution
Int. Immunol., August 13, 2007; (2007) dxm069v1.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
X.-c. Chen, R. Wang, X. Zhao, Y.-q. Wei, M. Hu, Y.-s. Wang, X.-w. Zhang, R. Zhang, L. Zhang, B. Yao, et al.
Prophylaxis against carcinogenesis in three kinds of unestablished tumor models via IL12-gene-engineered MSCs
Carcinogenesis, December 1, 2006; 27(12): 2434 - 2441.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Kinoshita, N. Shinomiya, S. Ono, H. Tsujimoto, T. Kawabata, A. Matsumoto, H. Hiraide, and S. Seki
Restoration of Natural IgM Production from Liver B Cells by Exogenous IL-18 Improves the Survival of Burn-Injured Mice Infected with Pseudomonas aeruginosa
J. Immunol., October 1, 2006; 177(7): 4627 - 4635.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
S Nagaraj, C Ziske, J Strehl, D Messmer, T Sauerbruch, and I. Schmidt-Wolf
Dendritic cells pulsed with alpha-galactosylceramide induce anti-tumor immunity against pancreatic cancer in vivo
Int. Immunol., August 1, 2006; 18(8): 1279 - 1283.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. R. Brutkiewicz
CD1d Ligands: The Good, the Bad, and the Ugly
J. Immunol., July 15, 2006; 177(2): 769 - 775.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. J. Ragin, N. Sahu, and A. August
Differential Regulation of Cytokine Production by CD1d-Restricted NKT Cells in Response to Superantigen Staphylococcal Enterotoxin B Exposure
Infect. Immun., January 1, 2006; 74(1): 282 - 288.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Margalit, S. A. Ghazala, R. Alper, E. Elinav, A. Klein, V. Doviner, Y. Sherman, B. Thalenfeld, D. Engelhardt, E. Rabbani, et al.
Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes
Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G917 - G925.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Kojo, K.-i. Seino, M. Harada, H. Watarai, H. Wakao, T. Uchida, T. Nakayama, and M. Taniguchi
Induction of Regulatory Properties in Dendritic Cells by V{alpha}14 NKT Cells
J. Immunol., September 15, 2005; 175(6): 3648 - 3655.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S.-Y. Ko, H.-J. Ko, W.-S. Chang, S.-H. Park, M.-N. Kweon, and C.-Y. Kang
{alpha}-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor
J. Immunol., September 1, 2005; 175(5): 3309 - 3317.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
T. Osada, M. A. Morse, H. K. Lyerly, and T. M. Clay
Ex vivo expanded human CD4+ regulatory NKT cells suppress expansion of tumor antigen-specific CTLs
Int. Immunol., September 1, 2005; 17(9): 1143 - 1155.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Biburger and G. Tiegs
{alpha}-Galactosylceramide-Induced Liver Injury in Mice Is Mediated by TNF-{alpha} but Independent of Kupffer Cells
J. Immunol., August 1, 2005; 175(3): 1540 - 1550.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Haraguchi, T. Takahashi, A. Matsumoto, T. Asai, Y. Kanda, M. Kurokawa, S. Ogawa, H. Oda, M. Taniguchi, H. Hirai, et al.
Host-Residual Invariant NK T Cells Attenuate Graft-versus-Host Immunity
J. Immunol., July 15, 2005; 175(2): 1320 - 1328.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. S. Bezbradica, A. K. Stanic, N. Matsuki, H. Bour-Jordan, J. A. Bluestone, J. W. Thomas, D. Unutmaz, L. Van Kaer, and S. Joyce
Distinct Roles of Dendritic Cells and B Cells in Va14Ja18 Natural T Cell Activation In Vivo
J. Immunol., April 15, 2005; 174(8): 4696 - 4705.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Crough, M. Nieda, and A. J. Nicol
Granulocyte Colony-Stimulating Factor Modulates {alpha}-Galactosylceramide-Responsive Human V{alpha}24+V{beta}11+ NKT Cells
J. Immunol., October 15, 2004; 173(8): 4960 - 4966.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. Ahmad and F. Alvarez
Role of NK and NKT cells in the immunopathogenesis of HCV-induced hepatitis
J. Leukoc. Biol., October 1, 2004; 76(4): 743 - 759.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Y. Setiady, P. Pramoonjago, and K. S. K. Tung
Requirements of NK Cells and Proinflammatory Cytokines in T Cell-Dependent Neonatal Autoimmune Ovarian Disease Triggered by Immune Complex
J. Immunol., July 15, 2004; 173(2): 1051 - 1058.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Nakagawa, T. Inui, I. Nagafune, Y. Tazunoki, K. Motoki, A. Yamauchi, M. Hirashima, Y. Habu, H. Nakashima, and S. Seki
Essential Role of Bystander Cytotoxic CD122+CD8+ T Cells for the Antitumor Immunity Induced in the Liver of Mice by {alpha}-Galactosylceramide
J. Immunol., June 1, 2004; 172(11): 6550 - 6557.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. Poirot, C. Benoist, and D. Mathis
Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity
PNAS, May 25, 2004; 101(21): 8102 - 8107.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Maeda, A. Shadeo, A. M. MacFadyen, and F. Takei
CD1d-Independent NKT Cells in {beta}2-Microglobulin-Deficient Mice Have Hybrid Phenotype and Function of NK and T Cells
J. Immunol., May 15, 2004; 172(10): 6115 - 6122.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Nieda, M. Okai, A. Tazbirkova, H. Lin, A. Yamaura, K. Ide, R. Abraham, T. Juji, D. J. Macfarlane, and A. J. Nicol
Therapeutic activation of V{alpha}24+V{beta}11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity
Blood, January 15, 2004; 103(2): 383 - 389.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
R. A. Campos, M. Szczepanik, A. Itakura, M. Akahira-Azuma, S. Sidobre, M. Kronenberg, and P. W. Askenase
Cutaneous Immunization Rapidly Activates Liver Invariant V{alpha}14 NKT Cells Stimulating B-1 B Cells to Initiate T Cell Recruitment for Elicitation of Contact Sensitivity
J. Exp. Med., December 15, 2003; 198(12): 1785 - 1796.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
I. F. Hermans, J. D. Silk, U. Gileadi, M. Salio, B. Mathew, G. Ritter, R. Schmidt, A. L. Harris, L. Old, and V. Cerundolo
NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells
J. Immunol., November 15, 2003; 171(10): 5140 - 5147.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Y. Crowe, A. P. Uldrich, K. Kyparissoudis, K. J. L. Hammond, Y. Hayakawa, S. Sidobre, R. Keating, M. Kronenberg, M. J. Smyth, and D. I. Godfrey
Glycolipid Antigen Drives Rapid Expansion and Sustained Cytokine Production by NK T Cells
J. Immunol., October 15, 2003; 171(8): 4020 - 4027.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. N. Baxevanis, A. D. Gritzapis, and M. Papamichail
In Vivo Antitumor Activity of NKT Cells Activated by the Combination of IL-12 and IL-18
J. Immunol., September 15, 2003; 171(6): 2953 - 2959.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Kenna, L. G. Mason, S. A. Porcelli, Y. Koezuka, J. E. Hegarty, C. O'Farrelly, and D. G. Doherty
NKT Cells from Normal and Tumor-Bearing Human Livers Are Phenotypically and Functionally Distinct from Murine NKT Cells
J. Immunol., August 15, 2003; 171(4): 1775 - 1779.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Hayakawa, S. Rovero, G. Forni, and M. J. Smyth
{alpha}-Galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis
PNAS, August 5, 2003; 100(16): 9464 - 9469.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
K. Kuwata, H. Watanabe, S.-Y. Jiang, T. Yamamoto, C. Tomiyama-Miyaji, T. Abo, T. Miyazaki, and M. Naito
AIM Inhibits Apoptosis of T Cells and NKT Cells in Corynebacterium-Induced Granuloma Formation in Mice
Am. J. Pathol., March 1, 2003; 162(3): 837 - 847.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Giaccone, C. J. A. Punt, Y. Ando, R. Ruijter, N. Nishi, M. Peters, B. M. E. von Blomberg, R. J. Scheper, H. J. J. van der Vliet, A. J. M. van den Eertwegh, et al.
A Phase I Study of the Natural Killer T-Cell Ligand {alpha}-Galactosylceramide (KRN7000) in Patients with Solid Tumors
Clin. Cancer Res., December 1, 2002; 8(12): 3702 - 3709.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Inui, R. Nakagawa, S. Ohkura, Y. Habu, Y. Koike, K. Motoki, N. Kuranaga, M. Fukasawa, N. Shinomiya, and S. Seki
Age-Associated Augmentation of the Synthetic Ligand- Mediated Function of Mouse NK1.1 Ag+ T Cells: Their Cytokine Production and Hepatotoxicity In Vivo and In Vitro
J. Immunol., December 1, 2002; 169(11): 6127 - 6132.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Ami, M. Kinoshita, A. Yamauchi, T. Nishikage, Y. Habu, N. Shinomiya, T. Iwai, H. Hiraide, and S. Seki
IFN-{gamma} Production from Liver Mononuclear Cells of Mice in Burn Injury As Well As in Postburn Bacterial Infection Models and the Therapeutic Effect of IL-18
J. Immunol., October 15, 2002; 169(8): 4437 - 4442.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
N. Y. Crowe, M. J. Smyth, and D. I. Godfrey
A Critical Role for Natural Killer T Cells in Immunosurveillance of Methylcholanthrene-induced Sarcomas
J. Exp. Med., July 1, 2002; 196(1): 119 - 127.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Z. Trobonjaca, A. Kroger, D. Stober, F. Leithauser, P. Moller, H. Hauser, R. Schirmbeck, and J. Reimann
Activating Immunity in the Liver. II. IFN-{beta} Attenuates NK Cell-Dependent Liver Injury Triggered by Liver NKT Cell Activation
J. Immunol., April 15, 2002; 168(8): 3763 - 3770.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.