Advanced search
1 file | 849.33 KB

Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator

(2008) Blood. 112(13). p.5046-5051
Author
Organization
Abstract
The Ly49 natural killer (NK)-cell receptor family comprises both activating and inhibitory members, which recognize major histocompatibility complex (MHC) class I or MHC class I-related molecules and are involved in target recognition. As previously shown, the Ly49E receptor fails to bind to a variety of soluble or cell-bound MHC class I molecules, indicating that its ligand is not an MHC class I molecule. Using BWZ. 36 reporter cells, we demonstrate triggering of Ly49E by the completely distinct, non-MHC-related protein urokinase plasminogen activator (uPA). uPA is known to be secreted by a variety of cells, including epithelial and hematopoietic cells, and levels are up-regulated during tissue remodeling, infections, and tumorigenesis. Here we show that addition of uPA to Ly49E-positive adult and fetal NK cells inhibits interferon-gamma secretion and reduces their cytotoxic potential, respectively. These uPA-mediated effects are Ly49E-dependent, as they are reversed by addition of anti-Ly49E monoclonal antibody and by down-regulation of Ly49E expression using RNA interference. Our results suggest that uPA, besides its established role in fibrinolysis, tissue remodeling, and tumor metastasis, could be involved in NK cell-mediated immune surveillance and tumor escape. (Blood. 2008; 112: 5046-5051)
Keywords
REPERTOIRE, CD94/NKG2, RECOGNITION, CYTOTOXICITY, IDENTIFICATION, EXPRESSION, MHC, MICE, RECEPTOR, NK CELLS

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 849.33 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Van Den Broeck, Tina, Frederick Stevenaert, Sylvie Taveirne, Veronique Debacker, CHRISTEL VANGESTEL, Bart Vandekerckhove, Tom Taghon, et al. 2008. “Ly49E-dependent Inhibition of Natural Killer Cells by Urokinase Plasminogen Activator.” Blood 112 (13): 5046–5051.
APA
Van Den Broeck, T., Stevenaert, F., Taveirne, S., Debacker, V., VANGESTEL, C., Vandekerckhove, B., Taghon, T., et al. (2008). Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator. Blood, 112(13), 5046–5051.
Vancouver
1.
Van Den Broeck T, Stevenaert F, Taveirne S, Debacker V, VANGESTEL C, Vandekerckhove B, et al. Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator. Blood. 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA: AMER SOC HEMATOLOGY; 2008;112(13):5046–51.
MLA
Van Den Broeck, Tina et al. “Ly49E-dependent Inhibition of Natural Killer Cells by Urokinase Plasminogen Activator.” Blood 112.13 (2008): 5046–5051. Print.
@article{604659,
  abstract     = {The Ly49 natural killer (NK)-cell receptor family comprises both activating and inhibitory members, which recognize major histocompatibility complex (MHC) class I or MHC class I-related molecules and are involved in target recognition. As previously shown, the Ly49E receptor fails to bind to a variety of soluble or cell-bound MHC class I molecules, indicating that its ligand is not an MHC class I molecule. Using BWZ. 36 reporter cells, we demonstrate triggering of Ly49E by the completely distinct, non-MHC-related protein urokinase plasminogen activator (uPA). uPA is known to be secreted by a variety of cells, including epithelial and hematopoietic cells, and levels are up-regulated during tissue remodeling, infections, and tumorigenesis. Here we show that addition of uPA to Ly49E-positive adult and fetal NK cells inhibits interferon-gamma secretion and reduces their cytotoxic potential, respectively. These uPA-mediated effects are Ly49E-dependent, as they are reversed by addition of anti-Ly49E monoclonal antibody and by down-regulation of Ly49E expression using RNA interference. Our results suggest that uPA, besides its established role in fibrinolysis, tissue remodeling, and tumor metastasis, could be involved in NK cell-mediated immune surveillance and tumor escape. (Blood. 2008; 112: 5046-5051)},
  author       = {Van Den Broeck, Tina and Stevenaert, Frederick and Taveirne, Sylvie and Debacker, Veronique and VANGESTEL, CHRISTEL and Vandekerckhove, Bart and Taghon, Tom and Matthys, Patrick and Plum, Jean and Held, Werner and Dewerchin, Mieke and Yokoyama, Wayne M. and Leclercq, Georges},
  issn         = {0006-4971},
  journal      = {Blood},
  keywords     = {REPERTOIRE,CD94/NKG2,RECOGNITION,CYTOTOXICITY,IDENTIFICATION,EXPRESSION,MHC,MICE,RECEPTOR,NK CELLS},
  language     = {eng},
  number       = {13},
  pages        = {5046--5051},
  publisher    = {AMER SOC HEMATOLOGY},
  title        = {Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator},
  url          = {http://dx.doi.org/10.1182/blood-2008-06-164350},
  volume       = {112},
  year         = {2008},
}

Altmetric
View in Altmetric
Web of Science
Times cited: