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Y Sakata, Y Eguchi, J Mimuro, M Matsuda and Y Sumi
Division of Hemostasis and Thrombosis, Jichi Medical School, Tokyo, Japan.
A monoclonal antibody (MoAb) to alpha 2-plasmin inhibitor designated JTPI-1
inhibited antiplasmin activity by interfering with formation of alpha
2-plasmin inhibitor (alpha 2-PI)-plasmin complex. With this MoAb, we
observed plasma clot lysis in vitro and evaluated the potential of JTPI-1
to serve as a new therapeutic agent for thrombolysis. After adding
125I-labeled fibrinogen to plasma, clots were made by adding thrombin and
calcium and were then resuspended in normal plasma containing various
concentrations of JTPI-1. The presence of JTPI-1 enhanced release of the
soluble 125I-labeled fibrin degradation fragment from the clots in a
dose-dependent manner. With tissue plasminogen activator (t-PA)-depleted
plasma, we showed that induction of clot lysis by JTPI-1 was dependent on
fibrin-bound endogenous t-PA. Regulation of fibrinolysis initiated on the
fibrin surface by fibrin- bound t-PA and plasminogen is mediated by alpha
2-PI cross-linked to fibrin by activated factor XIII. JTPI-1 bound to this
cross-linked alpha 2-PI neutralized its activity and induced partial
digestion of fibrin by plasmin. This resulted in additional binding of Glu-
plasminogen to fibrin during the incubation. When 1.2 mumol/L JTPI-1 and 5
U/mL exogenous t-PA were present in the suspending plasma, the rate of clot
lysis was essentially the same as that induced by 60 U/mL exogenous t-PA
alone. These results suggest that JTPI-1 may be useful in reducing the
amount of t-PA administered for thrombolytic therapy.
This article has been cited by other articles:
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| Copyright © 1989 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
