Urokinase receptor (uPAR, CD87) is a platelet receptor important for kinetics and TNF-induced endothelial adhesion in mice
| Autor: | Christian Vesin, Dominique Belin, Constance Barazzone, Fabienne Tacchini-Cottier, Pierre Francois Piguet, Yves Donati |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Plasmin
Neutrophils ddc:616.07 Mice Platelet Aprotinin skin and connective tissue diseases Receptor Endothelium Vascular/cytology/ metabolism Pulmonary Alveoli/blood supply Flow Cytometry Recombinant Proteins Tumor Necrosis Factor-alpha/antagonists & inhibitors/ metabolism/pharmacology Tumor necrosis factor alpha biological phenomena cell phenomena and immunity medicine.symptom Thrombocytopenia/metabolism/prevention & control Cardiology and Cardiovascular Medicine medicine.drug medicine.medical_specialty Cell Survival Inflammation Receptors Cell Surface Plasminogen Activators/ metabolism/pharmacology Chromium Radioisotopes/diagnostic use Injections Receptors Urokinase Plasminogen Activator Plasminogen Activators Recombinant Proteins/metabolism/pharmacology Physiology (medical) Internal medicine medicine Cell Adhesion Animals Aprotinin/pharmacology Neutrophils/metabolism Cell adhesion neoplasms business.industry Tumor Necrosis Factor-alpha Thrombocytopenia biological factors Chromium Radioisotopes Capillaries Urokinase receptor Mice Inbred C57BL Pulmonary Alveoli enzymes and coenzymes (carbohydrates) Kinetics Endocrinology Endothelium Vascular Receptors Cell Surface/ metabolism business |
| Zdroj: | Scopus-Elsevier Circulation, Vol. 99, No 25 (1999) pp. 3315-3321 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Background —Urokinase plasminogen activator receptor (uPAR, CD87) is a widely distributed 55-kD, glycoprotein I–anchored surface receptor. On binding of its ligand uPA, it is known to increase leukocyte adhesion and traffic. Using genetically deficient mice, we explored the role of uPAR in platelet kinetics and TNF-induced platelet consumption. Methods and Results —Anti-uPAR antibody stained platelets from normal (+/+) but not from uPAR −/− mice, as seen by fluorescence-activated cell sorter analysis. 51 Cr-labeled platelets from uPAR −/− donors survived longer than those from +/+ donors when injected into a +/+ recipient. Intratracheal TNF injection induced thrombocytopenia and a platelet pulmonary localization, pronounced in +/+ but absent in uPAR −/− mice. Aprotinin, a plasmin inhibitor, decreased TNF-induced thrombocytopenia. TNF injection markedly reduced the survival and increased the pulmonary localization of 51 Cr-labeled platelets from +/+ but not from uPAR −/− donors, indicating that it is the platelet uPAR that is critical for their response to TNF. As seen by electron microscopy, TNF injection increased the number of platelets and polymorphonuclear neutrophils (PMNs) in the alveolar capillaries of +/+ mice, whereas in uPAR −/− mice, platelet trapping was insignificant and PMN trapping was slightly reduced. Platelets within alveolar capillaries of TNF-injected mice were activated, as judged from their shape, and this was evident in +/+ but not in uPAR −/− mice. Conclusions —These results demonstrate for the first time the critical role of platelet uPAR for kinetics as well as for activation and endothelium adhesion associated with inflammation. |
| Databáze: | OpenAIRE |
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