Release of urokinase plasminogen activator receptor during urosepsis and endotoxemia.
BACKGROUND
The urokinase receptor (uPAR; CD87) is a multifunctional molecule involved in fibrinolysis, in proteolysis, in renal tubular functions, and in migration and adhesion of inflammatory cells to the site of infection.


METHODS
To gain insight into systemic and local release of uPAR and into its regulation during urosepsis, which is one of the leading causes of chronic renal failure, uPAR was measured in urine and plasma of healthy human controls (N = 20), patients with culture-proven urosepsis (N = 30), and healthy human volunteers intravenously injected with endotoxin (N = 7).


RESULTS
Patients had elevated uPAR levels in both plasma and urine. Three hours after endotoxin challenge in volunteers, there was also a significant increase of uPAR in plasma and in urine. The urine/plasma ratio for uPAR was highly elevated during urosepsis and experimental endotoxemia, suggesting local production in the kidney. Accordingly, damaged tubuli strongly expressed uPAR during pyelonephritis. Moreover, tubular epithelial cells produced uPAR in vitro, and this secretion was strongly up-regulated after stimulation with interleukin-1 beta or tumor necrosis factor-alpha.


CONCLUSIONS
We found that uPAR is released systemically and in the urinary tract during urosepsis and experimental endotoxemia. This systemic and renal production of uPAR during pyelonephritis may play a central role in eliminating the infection and protecting renal function.
Florquin
S
S
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.florquin@amc.uva.nl
van den Berg
J G
JG
Olszyna
D P
DP
Claessen
N
N
Opal
S M
SM
Weening
J J
JJ
van der Poll
T
T
D000328:Adult; D002461:Cell Line, Transformed; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced / Q000652:urine; D004731:Endotoxins / Q000633:toxicity; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D011704:Pyelonephritis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator; D018805:Sepsis / Q000097:blood* / Q000139:chemically induced / Q000652:urine
D004731:Endotoxins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C044101:endotoxin, Escherichia coli