Abstract
In recent papers it is reported that C1INA not only inhibits C1S and C1R, but also inhibits coagulation factors such as XIIa, XIa, kallikrein and plasmin, and Nagaki, et al. in 1977 described the fact that heparin promorted remarkably the inhibitory action of C1INA on C1S. Therefore, it is attempted in this paper to observe the effect of heparin on the inhibitory action of C1INA to coagulation factors, especially to plasma kallikrein, and the following results are obtained;
1) Normal human plasma shows one peak pattern in cross immunoelectrophoresis (CIEP) by the use of anti-C1INA serum. On the contrally, when heparin is added to normal plasma, three peaks appear in electrophoretic pattern, and this finding may indicate the complex formation of C1INA and heparin. If protamin sulfate is added to the mixture of plasma and heparin, the pattern of CIEP returns to one peak figure of normal plasma alone. These findings also suggest that the complex formation of C1INA and heparin is reversible.
2) The inhibitory action of heparin-C1INA complex against human plasma kallikrein in normal plasma and modified plasma including C1INA free plasma, AT III free plasma and both C1INA and AT III free plasma is studied by the use of chromogenic substrate (C-PK). In the cases of normal and AT III free plasma with heparin, the activity of plasma kallikrein reduces rapidly in proportion to the increase of heparin concentration, but in the cases of C1INA free plasma and C1INA-AT III free plasma there are no marked decrease of kallikrein activity in any concentration of heparin.
3) The addition of purified C1INA onto normal plasma decreases slightly the kallikrein activity, but the addition of heparin on the mixture above mentioned increases antikallikrein action of C1INA with enhancement of reaction rate.
4) The influences of heparin added to the mixture of purified human C1INA and plasma kallikrein are observed by chromogenic substrate technique and obtained the result, that heparin accelerates the formation of kallikrein-C1INA complex.
5) It is strongly suggested by the results mentioned above that the function of heparin in so-called heparin therapy for hypercoagulable state including DIC and hereditary angioneurotic edema may related with the accelerating antikallikrein action by heparin-C1INA complex formation.
