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Blood, 23 July 2009, Vol. 114, No. 4, pp. 860-870.
Prepublished online as a Blood First Edition Paper on April 27, 2009; DOI 10.1182/blood-2008-12-193524.


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PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS

Participation of the urokinase receptor in neutrophil efferocytosis

Young-Jun Park1,*, Gang Liu1,*, Yuko Tsuruta1, Emmanuel Lorne1,2, and Edward Abraham1

1 Department of Medicine, University of Alabama at Birmingham; and 2 Pole Anesthésie Réanimation, Centre Hospitalier Universitaire and Inserm, Amiens, France

The urokinase receptor (uPAR) plays an important role in regulation of fibronolysis, cell migration, and adhesion. In this study, we examined whether uPAR plays a role in modulating efferocytosis of neutrophils. Macrophages from uPAR–/– mice demonstrated enhanced ability to engulf viable wild-type (WT) neutrophils in vitro and in vivo in the lungs. The increased phagocytic activity of uPAR–/– macrophages was abrogated by incubation with soluble uPAR (suPAR), arginine-glycine-aspartic acid (RGD)–containing peptides, or anti-integrin antibodies. There was increased uptake of viable uPAR–/– neutrophils by WT macrophages. Incubation of uPAR–/– neutrophils with suPAR or anti-integrin antibodies diminished uptake by WT macrophages to baseline. Uptake of uPAR–/– neutrophils by uPAR–/– macrophages was not enhanced. However, incubation of uPAR–/– neutrophils or uPAR–/– macrophages, but not both, with suPAR enhanced the uptake of viable uPAR–/– neutrophils by uPAR–/– macrophages. The adhesion of WT neutrophils to uPAR–/– macrophages was higher than to WT macrophages. uPAR–/– neutrophils demonstrated increased adhesion to suPAR, which was abrogated by blocking of low-density lipoprotein related protein and integrins. Expression of uPAR on the surface of apoptotic neutrophils was reduced compared with levels on viable neutrophils. These results demonstrate a novel role for uPAR in modulating recognition and clearance of neutrophils.


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Related Article in Blood Online:

Efferocytosis: another function of uPAR
Francesco Blasi and Nicolai Sidenius
Blood 2009 114: 752-753. [Full Text] [PDF]



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F. Blasi and N. Sidenius
Efferocytosis: another function of uPAR
Blood, July 23, 2009; 114(4): 752 - 753.
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