Plasma plasminogen urokinase

Begum FD, Hogdall CK, Kjaer SK, Christensen L, Blaakaer J, Bock JE, et al. The prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) levels in stage III ovarian cancer patients. Anticancer Res 2004 24(3b) 1981-1985. 

Jl. Jensen, M. K., Riisbro, R., Holten-Andersen, M. N., et al.. Collagen metabolism and enzymes of the urokinase plasminogen activator system in chronic myeloproliferative disorders Correlation between plasma-soluble urokinase plasminogen activator receptor and serum markers for collagen metabolism. Eur. J. Haematol. 71, 276-282 (2003). 

Urokinase decreases the plasma plasminogen concentration and the proportion and concentration of high molecular weight fibrinogen complexes (3 ). Like streptokinase, urokinase may cause temperature elevation (25 ). 

Urokinase is a serine protease produced by the kidney and is found in both the plasma and urine. It is capable of proteolytically converting plasminogen into plasmin. Two variants of the enzyme have been isolated a 54 kDa species and a lower molecular mass (33 kDa) variant. The lower molecular mass form appears to be derived from the higher molecular mass moiety by proteolytic processing. Both forms exhibit enzymatic activity against plasminogen. 

The fibrin thrombus resulting from blood clotting (see p. 290) is dissolved again by plasmin, a serine proteinase found in the blood plasma. For this purpose, the precursor plasminogen first has to be proteolyti-cally activated by enzymes from various tissues. This group includes the plasminogen activator from the kidney (urokinase) and tissue plasminogen activator (t-PA) from vascular endothelia. By contrast, the plasma protein a2-antiplasmin, which binds to active plasmin and thereby inactivates it, inhibits fibrinolysis. 

Urokinase (Abbokinase) is a two-polypeptide chain serine protease that does not bind avidly to hbrin and that directly activates both circulating and hbrin-bound plasminogen. The plasma half-life of urokinase is approximately 10 to 20 minutes. Urokinase is derived from human cells and thus is not anhgenic. Urokinase produces a signihcant resolution of recent pulmonary emboli. 

Tincture of the dried seed, on agar plate at a concentration of 30 p,L/disc, was inactive on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Extract of 10 g plant material in 100 mL ethanol was used b Anticoagulation activity. Serpin BSZx (an inhibitor of trypsin and chemotrypsin) inhibited thrombin, plasma kallikrein, factor Vlla/tissue factor, and factor Xa at heparin-independent association rates. Only factor Xa turned a significant fraction of BSZx over as substrate. Activated protein C and leukocyte elastase were slowly inhibited by BSZx, whereas factor Xlla, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein, and elastase were not or only weakly affected. Trypsin from Fusarium was not inhibited, while interaction with subtilisin Carlsberg and Novo was rapid, but most BSZx was cleaved as a substrate L... 

Kofoed, K., et al. (2007) Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections a prospective study. Crit Care. 11, R38. 

Streptokinase is a protein (but not an enzyme in itself) synthesized by streptococci that combines with the proactivator plasminogen. This enzymatic complex catalyzes the conversion of inactive plasminogen to active plasmin. Urokinase is a human enzyme synthesized by the kidney that directly converts plasminogen to active plasmin. Plasmin itself cannot be used because naturally occurring inhibitors in plasma prevent its effects. However, the absence of inhibitors for urokinase and the streptokinase-proactivator complex permits their use clinically. Plasmin formed inside a thrombus by these activators is protected from plasma antiplasmins, which allows it to lyse the thrombus from within. 

Alteplase was the first commercially available recombinant tissue-type plasminogen activator (rt-PA) (25), It has a plasma half-life of less than five minutes and is metabolized by the liver, This agent was initially hailed as fibrin-specific unlike its precursors (urokinase and streptokinase). It was thought that this would result in a better safety profile, but this has not been born out in either the coronary or the peripheral experience, where actually there may be a higher bleeding risk as infusion time increases. Alteplase is currently indicated for use in the treatment of myocardial infarction, acute ischemic stroke, and pulmonary embolism. 

Treatment of manifest thrombosis under 1-ASP Is not standardized. Castamen et al. [118] were successful in one of two cases using a combination of fresh frozen plasma and s.c, heparin. Data on urokinase or recombinant tissue plasminogen activator fr-TPA) are unavailable to date. 

Ostrowski SR, Ullum H, Goka BQ, Hoyer-Hansen G, Obeng-Adjei G, Pedersen BK, et al. Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome. J Infect Dis 2005 191(8) 1331-1341. 

Ronne E, Pappot H, Grondahl-Hansen J, Hoyer-Hansen G, Plesner T, Hansen NE, et al. The receptor for urokinase plasminogen activator is present in plasma from healthy donors and elevated in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol 1995 89(3) 576-581. 

Pappot H, Hoyer-Hansen G, Ronne E, Hansen HH, Brunner N, Dano K, et al. Elevated plasma levels of urokinase plasminogen activator receptor in non-small cell lung cancer patients. Eur J Cancer 1997 33(6) 867-872. 

Riisbro R, Stephens RW, Brunner N, Christensen IJ, Nielsen HJ, Heilmann L, et al. Soluble urokinase plasminogen activator receptor in preoperatively obtained plasma from patients with gynecological cancer or benign gynecological diseases. Gynecol Oncol 2001 82(3) 523-531. 

Slot O, Brunner N, Locht H, Oxholm P, Stephens RW. Soluble urokinase plasminogen activator receptor in plasma of patients with inflammatory rheumatic disorders Increased concentrations in rheumatoid arthritis. Ann Rheum Dis 1999 58(8) 488-492. 

Streptokinase, anistreplase and urokinase are not well absorbed by fibrin thrombi and are called nonfibrin-selective. They convert plasminogen to plasmin in the circulation, which depletes plasma fibrinogen and induces a general hypocoagulant state. This does not reduce their local thrombolytic potential but increases the risk of bleeding. 

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