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Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo

May, A. E.
Kanse, S. M.
Lund, L. R.
Gisler, R. H.
Preissner, K. T.
Published in Journal of Experimental Medicine. 1998, vol. 188, no. 6, p. 1029-1037
Abstract The urokinase receptor (CD87; uPAR) is found in close association with beta 2 integrins on leukocytes. We studied the functional consequence of this association for leukocyte adhesion and migration. In vivo, the beta 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, beta 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 beta 2 integrin-stimulating pathway. These data indicate that beta 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.
Keywords AnimalsAntibodies, Monoclonal/pharmacologyAntigens, CD18/metabolism/ physiologyCell Adhesion/immunologyCell Movement/ immunologyEndothelium, Vascular/cytology/immunologyFemaleHumansLeukocytes/enzymology/ immunology/metabolismMiceMice, KnockoutMuscle, Smooth/cytology/immunologyPlasminogen Activators/ metabolismReceptors, Cell Surface/genetics/immunology/ physiologyReceptors, Urokinase Plasminogen ActivatorTumor Cells, CulturedUmbilical VeinsUrokinase-Type Plasminogen Activator/ metabolism
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PMID: 9743521
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