Urokinase Receptor (CD87) Regulates Leukocyte Recruitment via β2 Integrins In Vivo

AE May, SM Kanse, LR Lund, RH Gisler… - The Journal of …, 1998 - rupress.org
AE May, SM Kanse, LR Lund, RH Gisler, BA Imhof, KT Preissner
The Journal of experimental medicine, 1998rupress.org
The urokinase receptor (CD87; uPAR) is found in close association with β2 integrins on
leukocytes. We studied the functional consequence of this association for leukocyte
adhesion and migration. In vivo, the β2 integrin–dependent recruitment of leukocytes to the
inflamed peritoneum of uPAR-deficient mice was significantly reduced as compared with
wild-type animals. In vitro, β2 integrin–mediated adhesion of leukocytes to endothelium was
lost upon removal of uPAR from the leukocyte surface by phosphatidyl-inositol–specific …
The urokinase receptor (CD87; uPAR) is found in close association with β2 integrins on leukocytes. We studied the functional consequence of this association for leukocyte adhesion and migration. In vivo, the β2 integrin–dependent recruitment of leukocytes to the inflamed peritoneum of uPAR-deficient mice was significantly reduced as compared with wild-type animals. In vitro, β2 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 β2 integrin–stimulating pathway. These data indicate that β2 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.
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