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(Circulation. 1999;99:3315-3321.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Urokinase Receptor (uPAR, CD87) Is a Platelet Receptor Important for Kinetics and TNF-Induced Endothelial Adhesion in Mice

Pierre Francois Piguet, MD; Christian Vesin, BS; Yves Donati, BS; Fabienne Tacchini-Cottier, PhD; Dominique Belin, PhD; Constance Barazzone, MD

From the Departments of Pathology (P.F.P., C.V., Y.D., D.B., C.B.) and Pediatrics (C.B.), University of Geneva, and the WHO-IRTC, Institute of Biochemistry, University of Lausanne (F.T.-C.), Switzerland.

Correspondence to Pierre F. Piguet, MD, Department of Pathology, 1 rue M. Servet, CMU, 1211 Geneva, Switzerland. E-mail pierre.piguet{at}medecine.unige.ch

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.

Key Words: platelets • tumor necrosis factor • plasminogen activators

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