Abstract
AbstractThe 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.