| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Laboratory of Cellular Immunology, Division of Cellular and Gene Therapies, and
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
Although NO appears important in rodent immune responses, its
involvement in the human immune system is unclear. We report that human
NK cells express constitutive endothelial NO synthase mRNA and protein,
but not detectable levels of inducible NO synthase. They produce NO
following activation by coculture with target cells or cross-linking
with anti-CD16 mAb, and production is increased in the presence of
IL-2. N-monomethyl-L-arginine
(L-NMA), a NOS inhibitor, partially inhibited NK cell lysis
of four different target cells (<40% inhibition at 500 µM
L-NMA), but not granule release following coculture with
target cells, or Fas ligand induction following cross-linking with
anti-CD16 mAb. However, L-NMA augmented apoptosis of NK
cells induced by activation through CD16 ligation or coculture with
K562. An NO donor,
S-nitroso-N-acetylpenicillamine (SNAP),
suppressed apoptosis of NK cells induced by CD16 cross-linking or
coculture with target cells, suggesting that endogenous NO production
is involved in protection of NK cells from activation-induced
apoptosis, thereby maintaining NK activity. SNAP also suppressed, and
L-NMA enhanced, expression of TNF-
, reported to be
involved in activation-induced NK cell death, in response to CD16
cross-linking. Suppression of anti-CD16-induced apoptosis by SNAP
was reversed by the addition of rTNF-. DNA-binding activity of the
transcription factor, NF-AT, which is involved in TNF- induction
upon ligation of CD16, was inhibited by SNAP and enhanced by
L-NMA. Our results suggest that down-regulation of TNF-
expression, possibly due to suppression of NF-AT activation, is a
mechanism by which endogenous NO protects NK cells from
activation-induced apoptosis, and maintains lytic
capacity.
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
|
|
T. Inoue, Y. Suzuki, T. Yoshimaru, and C. Ra Nitric oxide protects mast cells from activation-induced cell death: the role of the phosphatidylinositol-3 kinase-Akt-endothelial nitric oxide synthase pathway J. Leukoc. Biol., May 1, 2008; 83(5): 1218 - 1229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wright, I. S. Singh, J. D. Hasday, I. K. Farrance, G. Hall, A. S. Cross, and T. B. Rogers Endotoxin stress-response in cardiomyocytes: NF-kappa B activation and tumor necrosis factor-alpha expression Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H872 - H879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tsuyuki, J. A. Horvath-Arcidiacono, and E. T. Bloom Effect of Redox Modulation on Xenogeneic Target Cells: The Combination of Nitric Oxide and Thiol Deprivation Protects Porcine Endothelial Cells from Lysis by IL-2-Activated Human NK Cells J. Immunol., March 15, 2001; 166(6): 4106 - 4114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Salvucci, M. Carsana, I. Bersani, G. Tragni, and A. Anichini Antiapoptotic Role of Endogenous Nitric Oxide in Human Melanoma Cells Cancer Res., January 1, 2001; 61(1): 318 - 326. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
