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K Kurosawa-Ohsawa, M Kimura, A Kume-Iwaki, T Tanaka and S Tanaka
Pharma Research Laboratories, Hoechst Japan Ltd, Saitama.
Protein C (PC) is considered to be an important regulator of blood
coagulation and fibrinolysis. During the production of monoclonal
antibodies (MoAbs) against human PC in mouse ascitic fluid, one hybridoma
was found to induce heavy thrombus in mice, resulting in severe hemorrhage.
Intravenous infusion of the purified MoAb (PC01) from this hybridoma also
caused thrombosis in mice. The crossreacting substance was then isolated
from mouse plasma with PC01 immunoaffinity column, which was identified as
mouse PC by several criteria. Mouse PC prolonged the activated partial
thromboplastin time of mouse plasma, and PC01 neutralized this in vitro
anti-coagulant activity. Therefore, heavy thrombosis observed in
PC01-treated mice is likely to be ascribed to the defect of PC caused by
PC01.
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