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Nonradical oxidants of the phagocyte type induce the activation of plasmatic single chain- urokinase

Thrombosis Research
Publication Date
DOI: 10.1016/s0049-3848(05)80009-x
  • Single Chain (Pro) Urokinase
  • Oxidants
  • Phagocytes
  • Fibrinolysis
  • Regulation
  • Singlet Molecular Oxygen
  • Biology
  • Medicine


Abstract Single chain- urokinase (scu-PA) is the proenzyme of the plasminogen activator urokinase (tcu-PA). In human blood scu-PA is of great stability. Activated phagocytes generate large amounts of single chain- urokinase and of reactive oxidants (chloramines and HOCl). Since these cells participate in physiologic fibrinolysis, we were interested in the interaction between plasmatic scu-PA and chloramines. The oxidants dose dependently induce the activation of plasmatic scu-PA. Optimal activation of scu-PA occurs at about 3 – 5 mmol/l of chloramine-T. The findings suggest a control mechanism of scu-PA stability/ activity by oxidatively modifiable plasma proteins, such as a-2-antiplasmin. The oxidation mechanism seems to be mediated by singlet molecular oxygen, an excited oxygen species. Basing on this scu-PA/ oxidant synergism a sensitive and fast functional assay of scu-PA in human plasma is presented. Plasmatic inhibitors normally interfering with functional scu-PA measurements are inactivated by addition of chloramine-T, imitating the physiological oxidants generated by activated phagocytes. The scu-PA concentration in plasma of n= 36 healthy individuals has been determined to be 5.8 ± 1.6 ng/ml. The lower detection limit of plasma scu-PA by the procedure described is about 1.5 ng/ ml of plasma. By means of this technique scu-PA concentration during thrombolytic therapy can be measured within minutes in undiluted (direct) plasma samples, allowing adjustments of the scu-PA dosage. The present study gives further credence for a role of singlet molecular oxygen, possibly a new type of locally acting hormones (autacoid), in the regulation of the fibrinolytic pathway.

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