Fast-acting plasmin inhibitor in human plasma

Area of Science:

• Biochemistry
• Protease Inhibitors
• Fibrinolysis

Background:

• Plasmin is the key enzyme in fibrinolysis, responsible for breaking down blood clots.
• Regulation of plasmin activity is crucial for maintaining hemostasis and preventing excessive bleeding or clotting.
• Previous understanding of plasmin inhibition in human plasma was incomplete.

Purpose of the Study:

• To characterize a newly discovered inhibitor of plasmin in human plasma.
• To elucidate the mechanism of inhibition and the role of this inhibitor in physiological and pathological conditions.
• To explore the potential diagnostic applications of the plasmin-antiplasmin interaction.

Main Methods:

• Purification of the alpha 2-glycoprotein inhibitor from human plasma.
• Determination of molecular weight and concentration.
• Biochemical analysis of the interaction between the inhibitor and plasmin, including stoichiometry and reaction site.
• Assessment of inhibitory activity against other proteases in vitro.
• Investigation of the inhibitor's role in fibrinolysis associated with malignant cells.

Main Results:

• A fast-acting alpha 2-glycoprotein inhibitor of plasmin was purified, with a molecular weight of 65,000-70,000 daltons and a plasma concentration of 1 muM.
• The inhibitor forms a 1:1 stoichiometric complex with plasmin, reacting with the B chain (light chain) containing the active center, leading to complete inactivation.
• While showing slow interactions with trypsin and urokinase in vitro, its in vivo role as an inhibitor of other proteases appears negligible.
• This antiplasmin is the sole plasma protein capable of inhibiting fibrinolysis linked to transformed or malignant cells.
• The plasmin-antiplasmin complex exhibits neoantigenic structures, suggesting potential for immunochemical detection of fibrinolytic system activation.

Conclusions:

• The identified alpha 2-glycoprotein, termed antiplasmin, is the principal physiological inhibitor of plasmin in human plasma.
• Antiplasmin plays a critical role in regulating fibrinolysis and is uniquely positioned to counteract fibrinolytic activity associated with malignancy.
• The neoantigenic properties of the plasmin-antiplasmin complex offer a promising avenue for developing diagnostic tools to monitor fibrinolytic system activation.