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Thromb Haemost 1993; 69(01): 050-055
DOI: 10.1055/s-0038-1651547
Original Article
Fibrinolysis
Schattauer GmbH Stuttgart

A Hybrid Plasminogen Activator Binds to the u-PA Receptor and Has a Reduced Thrombolytic Potency In Vivo

Fred A M Asselbergs
The Biotechnology Department, CIBA-GEIGY Ltd. K681.4.42, Basle, Switzerland
,
Rolf Bürgi
The Biotechnology Department, CIBA-GEIGY Ltd. K681.4.42, Basle, Switzerland
,
Jessica Hamerman
The Biotechnology Department, CIBA-GEIGY Ltd. K681.4.42, Basle, Switzerland
,
Jutta Heim
The Biotechnology Department, CIBA-GEIGY Ltd. K681.4.42, Basle, Switzerland
,
Jan van Oostrum
The Biotechnology Department, CIBA-GEIGY Ltd. K681.4.42, Basle, Switzerland
,
Giancarlo Agnelli
1   The Instituto di Semiotica Medica, University of Perugia, Perugia, Italy
› Institutsangaben
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Publikationsverlauf

Received 16. April 1992

Accepted after revision 11. September 1992

Publikationsdatum:
04. Juli 2018 (online)

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Summary

Fibrinolytic properties of four hybrids of u-PA and t-PA, all containing the u-PA growth factor domain and binding to recombinant human u-PA receptor expressed in CHO cells, were compared. Highest fibrin stimulation was observed with uK2tPA which when compared to t-PA in the rabbit system, had a considerably prolonged circulatory half-life in vivo. Compared to an equimolar dose of t-PA, 0.4 mg/kg uK2tPA caused a similar consumption of α2-antiplasmin and fibrinogen and a considerably greater prolongation of the ex-vivo blood clotting time. Nevertheless, this dose of uK2tPA was inactive in the jugular vein thrombosis assay. This lack of thrombolytic activity is presumably due to the presence of a functional u-PA growth factor domain, which in binding uK2tPA to cellular blood elements possibly retards its penetration into the blood clot and in this manner could neutralize the potential thrombolytic activity of the t-PA kringle 2 and protease domains in uK2tPA.

 

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