Urokinase-type plasminogen activator receptor plays a role in neutrophil migration during lipopolysaccharide-induced peritoneal inflammation but not during Escherichia coli-induced peritonitis.
BACKGROUND
Urokinase-type plasminogen activator receptor (uPAR) is expressed on many different cells, including leukocytes. uPAR has been implicated to play a role in neutrophil migration to sites of inflammation.


METHODS
To determine the role that uPAR plays in neutrophil recruitment in response to bacterial products or intact bacteria, uPAR gene-deficient (uPAR(-/-)) and wild-type (wt) mice were injected intraperitoneally with either Escherichia coli or lipopolysaccharide (LPS) derived from this bacterium.


RESULTS
uPAR(-/-) mice demonstrated a decreased LPS-induced neutrophil migration into peritoneal lavage fluid, whereas the chemokine and cytokine response was unaltered. In contrast, during E. coli-induced peritonitis, uPAR(-/-) mice had a normal neutrophil migration into the primary site of infection. The unaltered neutrophil trafficking in uPAR(-/-) mice during bacterial infection was corroborated by histological assessment of liver and lung tissue and myeloperoxidase levels in tissue homogenates. uPAR(-/-) mice displayed slightly but significantly lower bacterial loads in the peritoneal cavity, together with a decreased dissemination to the circulation early during the infection.


CONCLUSIONS
These data suggest that uPAR, in part, mediates neutrophil migration into the peritoneal cavity on local instillation of LPS but that this function of uPAR can be compensated for during peritonitis caused by intact E. coli.
Renckens
Rosemarijn
R
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. r.renckens@amc.uva.nl
Roelofs
Joris J T H
JJ
Florquin
Sandrine
S
van der Poll
Tom
T
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000502:physiology*; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000473:pathology*; D010538:Peritonitis / Q000139:chemically induced / Q000382:microbiology / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator
D008070:Lipopolysaccharides; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator