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

Autor: Roland H. Gisler, Leif R. Lund, Klaus T. Preissner, Beat A. Imhof, Sandip M. Kanse, Andreas E. May
Jazyk: angličtina
Rok vydání: 1998
Předmět:
Umbilical Veins
Cell Adhesion/immunology
Receptors
Cell Surface/genetics/immunology/ physiology
Leukocytes/enzymology/ immunology/metabolism
ddc:616.07
Mice
Plasminogen Activators/ metabolism
Cell Movement
Leukocytes
Tumor Cells
Cultured
Immunology and Allergy
skin and connective tissue diseases
Receptor
Mice
Knockout
Antibodies
Monoclonal
Antigens
CD18/metabolism/ physiology
Articles
Adhesion
endothelial cells
β2 integrin
medicine.anatomical_structure
Female
medicine.symptom
leukocyte
Muscle
Smooth/cytology/immunology
Endothelium
Immunology
Integrin
Endothelium
Vascular/cytology/immunology
Receptors
Cell Surface
Inflammation
Biology
Receptors
Urokinase Plasminogen Activator
Plasminogen Activators
In vivo
Cell Adhesion
urokinase receptor
medicine
Animals
Humans
Cell adhesion
neoplasms
Cell Movement/ immunology
Muscle
Smooth
Urokinase-Type Plasminogen Activator
Molecular biology
biological factors
Antibodies
Monoclonal/pharmacology
Urokinase receptor
inflammation
CD18 Antigens
biology.protein
Endothelium
Vascular
Urokinase-Type Plasminogen Activator/ metabolism
Zdroj: Journal of Experimental Medicine, Vol. 188, No 6 (1998) pp. 1029-1037
The Journal of Experimental Medicine
ISSN: 0022-1007
Popis: 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.
Databáze: OpenAIRE
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