| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Laboratory of Tumor Immunology, Scientific Institute San Raffaele, Milan, Italy;
Laboratory of Clinical Pathology, National Institute for Cancer Research, Genoa, Italy; and
Laboratory of Immunopathology, National Institute for Cancer Research and Advanced Biotechnology Center, Genoa, Italy
Herein we show that functional phenylalkylamine-sensitive L-type calcium channels are expressed by human NK cells and are involved in the killing of tumor targets. Blocking of these channels by phenylalkylamine drugs does not affect effector/target cell binding but inhibits the release of serine esterases responsible for cytotoxicity. Interestingly, treatment of NK cells with HIV-1 Tat, which is known to affect several calcium-mediated events in immune cells, impairs their cytotoxic activity. In addition, Tat inhibits the rise in intracellular free calcium concentration upon cross-linking of the adhesion molecule CD11a, engaged during effector/target cell interaction, and the activation molecule CD16. Exogenous Tat does not influence NK-target cell binding but prevents NK cell degranulation. We propose that the molecular structure(s) on NK cells mediating the inhibitory effects HIV-1 Tat belong to L-type calcium channels, based on three lines of evidence: 1) binding of phenylalkylamine derivatives to these channels is cross-inhibited by Tat; 2) L-type calcium channels from NK cell lysates bind to Tat linked to Sepharose columns; 3) the inhibitory effect of HIV-1 Tat on NK cell function is prevented by the agonist of L-type calcium channels, Bay K 8644. Altogether, these results suggest that exogenous Tat is deeply involved in the impairment of NK cell function during HIV-1 infection.
This article has been cited by other articles:
|
|
 |
|
  B. Majumder, N. J. Venkatachari, S. O'Leary, and V. Ayyavoo Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells J. Virol., July 15, 2008; 82(14): 7189 - 7200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Iannello, O. Debbeche, S. Samarani, and A. Ahmad Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination J. Leukoc. Biol., July 1, 2008; 84(1): 27 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Semino, J. Ceccarelli, L. V. Lotti, M. R. Torrisi, G. Angelini, and A. Rubartelli The maturation potential of NK cell clones toward autologous dendritic cells correlates with HMGB1 secretion J. Leukoc. Biol., January 1, 2007; 81(1): 92 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Gomes, M. Savignac, M. D. Cabral, P. Paulet, M. Moreau, C. Leclerc, R. Feil, F. Hofmann, J.-C. Guery, G. Dietrich, et al. The cGMP/Protein Kinase G Pathway Contributes to Dihydropyridine-sensitive Calcium Response and Cytokine Production in TH2 Lymphocytes J. Biol. Chem., May 5, 2006; 281(18): 12421 - 12427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Poggi, C. Prevosto, A.-M. Massaro, S. Negrini, S. Urbani, I. Pierri, R. Saccardi, M. Gobbi, and M. R. Zocchi Interaction between Human NK Cells and Bone Marrow Stromal Cells Induces NK Cell Triggering: Role of NKp30 and NKG2D Receptors J. Immunol., November 15, 2005; 175(10): 6352 - 6360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Poggi, S. Negrini, M. R. Zocchi, A.-M. Massaro, L. Garbarino, S. Lastraioli, L. Gargiulo, L. Luzzatto, and R. Notaro Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral-blood T cells expressing activating isoforms of inhibiting superfamily receptors Blood, October 1, 2005; 106(7): 2399 - 2408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Zocchi, P. Contini, M. Alfano, and A. Poggi Pertussis Toxin (PTX) B Subunit and the Nontoxic PTX Mutant PT9K/129G Inhibit Tat-Induced TGF-{beta} Production by NK Cells and TGF-{beta}-Mediated NK Cell Apoptosis J. Immunol., May 15, 2005; 174(10): 6054 - 6061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Poggi, A.-M. Massaro, S. Negrini, P. Contini, and M. R. Zocchi Tumor-Induced Apoptosis of Human IL-2-Activated NK Cells: Role of Natural Cytotoxicity Receptors J. Immunol., March 1, 2005; 174(5): 2653 - 2660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Savignac, B. Gomes, A. Gallard, S. Narbonnet, M. Moreau, C. Leclerc, P. Paulet, B. Mariame, P. Druet, A. Saoudi, et al. Dihydropyridine Receptors Are Selective Markers of Th2 Cells and Can Be Targeted to Prevent Th2-Dependent Immunopathological Disorders J. Immunol., May 1, 2004; 172(9): 5206 - 5212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Spaggiari, P. Contini, A. Dondero, R. Carosio, F. Puppo, F. Indiveri, M. R. Zocchi, and A. Poggi Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction Blood, December 1, 2002; 100(12): 4098 - 4107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Spaggiari, P. Contini, R. Carosio, M. Arvigo, M. Ghio, D. Oddone, A. Dondero, M. R. Zocchi, F. Puppo, F. Indiveri, et al. Soluble HLA class I molecules induce natural killer cell apoptosis through the engagement of CD8: evidence for a negative regulation exerted by members of the inhibitory receptor superfamily Blood, March 1, 2002; 99(5): 1706 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Poggi, R. Carosio, G. M. Spaggiari, C. Fortis, G. Tambussi, G. Dell'Antonio, E. Dal Cin, A. Rubartelli, and M. R. Zocchi NK Cell Activation by Dendritic Cells Is Dependent on LFA-1-Mediated Induction of Calcium-Calmodulin Kinase II: Inhibition by HIV-1 Tat C-Terminal Domain J. Immunol., January 1, 2002; 168(1): 95 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gardella, C. Andrei, L. V. Lotti, A. Poggi, M. R. Torrisi, M. R. Zocchi, and A. Rubartelli CD8+ T lymphocytes induce polarized exocytosis of secretory lysosomes by dendritic cells with release of interleukin-1{beta} and cathepsin D Blood, October 1, 2001; 98(7): 2152 - 2159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Gao, J. Golob, V. M. Tanavde, C. I. Civin, R. G. Hawley, and L. Cheng High Levels of Transgene Expression Following Transduction of Long-Term NOD/SCID-Repopulating Human Cells with a Modified Lentiviral Vector Stem Cells, May 1, 2001; 19(3): 247 - 259. [Abstract] [Full Text]
|
|
|
|
|
|
A. Badou, Y. Bennasser, M. Moreau, C. Leclerc, M. Benkirane, and E. Bahraoui Tat Protein of Human Immunodeficiency Virus Type 1 Induces Interleukin-10 in Human Peripheral Blood Monocytes: Implication of Protein Kinase C-Dependent Pathway J. Virol., November 15, 2000; 74(22): 10551 - 10562. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. C. Gallo Tat as one key to HIV-induced immune pathogenesis and Pat toxoid as an important component of a vaccine PNAS, July 20, 1999; 96(15): 8324 - 8326. [Full Text] [PDF]
|
|
|
|
|
|
G. Angelini, S. Gardella, M. Ardy, M. R. Ciriolo, G. Filomeni, G. Di Trapani, F. Clarke, R. Sitia, and A. Rubartelli From the Cover: Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation PNAS, February 5, 2002; 99(3): 1491 - 1496. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
