title: Participation of the urokinase receptor in neutrophil efferocytosis.
abstract: 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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 1808 7th Avenue South, Birmingham, AL, USA.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Park
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuruta
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lorne
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005260:Female; D016023:Integrins / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis / Q000235:genetics*; D011485:Protein Binding; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D000954:Antigens, Surface; D016023:Integrins; D055293:Receptors, Urokinase Plasminogen Activator