Release of urokinase plasminogen activator receptor during urosepsis and endotoxemia

Background. The urokinase receptor (uPAR; CD87) is a multifunctional molecu le involved in fibrinolysis, in proteolysis, in renal tubular functions, an d 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 i ts regulation during urosepsis, which is one of the leading causes of chron ic renal failure, uPAR was measured in urine and plasma of healthy human co ntrols (N = 20), patients with culture-proven urosepsis (N = 30), and healt hy 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 w as highly elevated during urosepsis and experimental endotoxemia, suggestin g local production in the kidney. Accordingly, damaged tubuli strongly expr essed uPAR during pyelonephritis. Moreover, tubular epithelial cells produc ed uPAR in vitro, and this secretion was strongly up-regulated after stimul ation 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 ren al production of uPAR during pyelonephritis may play a central role in elim inating the infection and protecting renal function.