| First Author | Van Den Broeck T | Year | 2008 |
| Journal | Blood | Volume | 112 |
| Issue | 13 | Pages | 5046-51 |
| PubMed ID | 18784372 | Mgi Jnum | J:143621 |
| Mgi Id | MGI:3828249 | Doi | 10.1182/blood-2008-06-164350 |
| Citation | Van Den Broeck T, et al. (2008) Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator. Blood 112(13):5046-51 |
| abstractText | 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. |
