Urokinase does not upregulate the vascular endothelial cell-mediated inflammatory response.
OBJECTIVE
Urokinase is used clinically for thrombolysis, but little is known of its direct effect on vascular endothelial cells. The following experiments were preformed to assess the in vitro effects of urokinase on vascular endothelial cell growth, adhesion molecule expression, and interaction with lymphocytes, polymorphonuclear leukocytes, and platelets.


METHODS
Commercially available human umbilical vein endothelial cells (HUVEC) were cultured with varying concentrations of urokinase (0 to 10,000 IU/ml) (clinical dosage, < or = 500 IU/ml). HUVEC viability was determined from 1 to 4 days. HUVECs were incubated with urokinase (0 to 2000 IU/ml) from 4 to 72 hours. Adherence of 51-chromium-labeled polymorphonuclear leukocytes, platelets, or lymphocytes was then quantitated. In separate experiments HUVEC adhesion molecule expression (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or endothelial leukocyte adhesion molecule-1) was determined by flow cytometry.


RESULTS
There was a decrease of HUVEC viability at suprapharmacologic urokinase concentrations of > or = 2000 IU/ml compared with nontreated control samples (0 IU/ml, 73% +/- 2%, 2000 IU/ml, 60.5% +/- 1.9%, p < 0.05) presumably because of drug toxicity. There was no significantly increased polymorphonuclear leukocyte, lymphocyte, or platelet adhesion to urokinase-treated HUVEC monolayes at any time point. This was also true for each adhesion molecule tested.


CONCLUSIONS
Urokinase at clinically relevant concentrations (< or = 500 IU/ml) did not affect endothelial cell viability or growth, nor did it upregulate adhesion molecule expression or cellular adhesion associated with the cell vascular inflammatory response. It is therefore implied that the use of urokinase in vivo similarly would not initiate the vascular inflammatory response.
Rhodes
J M
JM
Department of Surgery, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center 17033, USA.
Tilberg
A F
AF
Gifford
R R
RR
D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014568:Urokinase-Type Plasminogen Activator