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Urokinase receptor (CD87) regulates leukocyte recruitment via � 2 integrins (1998)
| Citations: | 26 - 1 self |
BibTeX
@MISC{May98urokinasereceptor,
author = {E. May and Ip M. Kanse and Leif R. Lund and H. Gisler and Beat A. Imhof and Klaus T. Preissner},
title = {Urokinase receptor (CD87) regulates leukocyte recruitment via � 2 integrins},
year = {1998}
}
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Abstract
The urokinase receptor (CD87; uPAR) is found in close association with �2 integrins on leukocytes. We studied the functional consequence of this association for leukocyte adhesion and migration. In vivo, the �2 integrin–dependent recruitment of leukocytes to the inflamed peritoneum of uPAR-deficient mice was significantly reduced as compared with wild-type animals. In vitro, �2 integrin–mediated adhesion of leukocytes to endothelium was lost upon removal of uPAR from the leukocyte surface by phosphatidyl-inositol–specific phospholipase C. Leukocyte adhesion was reconstituted when soluble intact uPAR, but not a truncated form lacking the uPA-binding domain, was allowed to reassociate with the cell surface. uPAR ligation with a monoclonal antibody induced adhesion of monocytic cells and neutrophils to vascular endothelium by six- to eightfold, whereas ligation with inactivated uPA significantly reduced cell-to-cell adhesion irrespective of the �2 integrin–stimulating pathway. These data indicate that �2 integrin–mediated leukocyte–endothelial cell interactions and recruitment to inflamed areas require the presence of uPAR and define a new phenotype for uPAR-deficient mice. Moreover, uPAR ligation differentially modulates leukocyte adhesion to endothelium and provides novel targets for therapeutic strategies in inflammation-related vascular pathologies.
Keyphrases
urokinase receptor leukocyte recruitment leukocyte adhesion upar ligation upar-deficient mouse new phenotype inflammation-related vascular pathology integrin dependent recruitment vascular endothelium cell-to-cell adhesion irrespective phosphatidyl-inositol specific phospholipase cell surface monocytic cell inflamed peritoneum leukocyte endothelial cell interaction novel target whereas ligation inactivated upa functional consequence close association wild-type animal therapeutic strategy leukocyte surface truncated form monoclonal antibody induced adhesion upa-binding domain
