Cl Inhibitor Research Articles

Inactivation of Purified Human α2-Antiplasmin and Purified Human C1 Inhibitor by Synthetic Fibrinolytic Agents

Abstract3-Hydroxypropyl flufenamide (Flu-HPA) is one of a series of flufenamic acid derivatives that enhances blood clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The profibrinolytic activity of Flu-HPA in clot lysis assays was found to be dependent on plasminogen. The influence of Flu-HPA on the ability of purified α2-antiplasmin to inhibit purified plasmin was studied. Plasmin activity was determined using 125l-fibrin plates or the spectrophotometric tripeptide substrate, Val-Leu-Lys-paranitroanilide. At Flu-HPA concentrations greater than 1 mM, the inhibitory activity of α2-antiplasmin was abolished in a time-dependent and concentration-dependent manner. The influence of Flu-HPA on the ability of purified C$$ inhibitor to inhibit purified plasma kallikrein and β-Factor XIIa was also studied. Cl inhibitor activity was abolished by Flu-HPA at concentrations greater than 2 mM. Notably, Flu-HPA up to 60 mM did not affect the amidolytic activities of plasmin, kallikrein, or β-Factor XIIa. Flu-HPA did not release enzyme activity from preformed complexes of either α2-antiplasmin and plasmin or Cl inhibitor and kallikrein. A water-soluble derivative of flufenamic acid, N-flufenamyl-glutamic acid, also inactivated α2-antiplasm and C$$ inhibitor. This inactivation was shown to be reversible. These results indicate that synthetic fibrinolytic compounds such as flufenamic acid derivatives may promote fibrinolysis by directly inactivating α2-antiplasmin and C$$ inhibitor.

Immunological studies of plasma protease inhibitors associated with human blood platelets.

Abstract Associations between whole human platelets and plasma protease inhibitors were studied by direct immunofluorescence techniques. Tested conjugates of anti-human antisera to α 1 -antitrypsin, α 2 -macroglobulin, α 1 -antichymotrypsin, inter-α-trypsin inhibitor, Cl inhibitor and antithrombin III were used. Only α 1 -antitrypsin and Cl inhibitor were found to be associated with platelets. The biological role of platelet-associated protease inhibitors is discussed.

C1 inhibitor: evidence for decreased hepatic synthesis in hereditary angioneurotic edema.

Although the Cl inhibitor was detected in 5 to 10 percent of normal hepatic parenchymal cells by means of the immunofluorescent technique, none was seen in liver biopsies from two individuals with hereditary angioneurotic edema having low concentrations of Cl inhibitor in the serum. In contrast, the percentages of cells which reacted with fluorescent antiserums to C4 and transferrin were normal. These data suggest that in most subjects with hereditary angioneurotic edema, there is decreased synthesis of the C1 inhibitor but normal synthesis of C4, and that the disease results from this biosynthetic error.