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

Details

Serval ID
serval:BIB_8F39325DFF7E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator.
Journal
Blood
Author(s)
Van Den Broeck T., Stevenaert F., Taveirne S., Debacker V., Vangestel C., Vandekerckhove B., Taghon T., Matthys P., Plum J., Held W., Dewerchin M., Yokoyama W.M., Leclercq G.
ISSN
1528-0020[electronic]
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
112
Number
13
Pages
5046-5051
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
Keywords
Animals, Cytotoxicity, Immunologic, Immunologic Surveillance, Interferon-gamma/secretion, Killer Cells, Natural/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, NK Cell Lectin-Like Receptor Subfamily A/physiology, Tumor Escape, Urokinase-Type Plasminogen Activator/physiology
Pubmed
Web of science
Open Access
Yes
Create date
15/01/2010 14:54
Last modification date
20/08/2019 14:52
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