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.
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.
Authors: T K Outinen; S Mäkelä; R Huttunen; N Mäenpää; D Libraty; A Vaheri; J Mustonen; J Aittoniemi Journal: J Intern Med Date: 2014-05-14 Impact factor: 8.989
Authors: Paulo Rabna; Andreas Andersen; Christian Wejse; Ines Oliveira; Victor Francisco Gomes; Maya Bonde Haaland; Peter Aaby; Jesper Eugen-Olsen Journal: PLoS One Date: 2012-08-28 Impact factor: 3.240
Authors: Yara Backes; Koenraad F van der Sluijs; David P Mackie; Frank Tacke; Alexander Koch; Jyrki J Tenhunen; Marcus J Schultz Journal: Intensive Care Med Date: 2012-06-16 Impact factor: 17.440