UNIGE document Scientific Article
previous document  unige:11515  next document
add to browser collection

Urokinase receptor (uPAR, CD87) is a platelet receptor important for kinetics and TNF-induced endothelial adhesion in mice

Piguet, P. F.
Published in Circulation. 1999, vol. 99, no. 25, p. 3315-3321
Abstract 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. 51Cr-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 51Cr-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.
Keywords AnimalsAprotinin/pharmacologyCapillariesCell AdhesionCell SurvivalChromium Radioisotopes/diagnostic useEndothelium, Vascular/cytology/ metabolismFlow CytometryInjectionsKineticsMiceMice, Inbred C57BLNeutrophils/metabolismPlasminogen Activators/ metabolism/pharmacologyPulmonary Alveoli/blood supplyReceptors, Cell Surface/ metabolismReceptors, Urokinase Plasminogen ActivatorRecombinant Proteins/metabolism/pharmacologyThrombocytopenia/metabolism/prevention & controlTumor Necrosis Factor-alpha/antagonists & inhibitors/ metabolism/pharmacology
Stable URL http://archive-ouverte.unige.ch/unige:11515
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://circ.ahajournals.org/cgi/reprint/99/25/3315.pdf
PMID: 10385508
Research group Rôle du stress oxydatif dans les maladies aiguës et chroniques pulmonaires (182)
151 hits and 0 download since 2010-08-27
Export document
Format :
Citation style :