Plasma Clearance of Human Antiproteinase/Proteinase Complexes

Abstract

Evidence has been obtained, though frequently by an indirect manner, showing that α₂M/proteinase complexes are quickly removed from circulation. Thus Nilehn and Ganrot [1] succeeded in achieving activation of the entire plasma plasminogen pool by massive streptokinase therapy. Plasmin was mainly recovered as an α₂M/plasmin complex which disappeared from circulation within 24 h. During this period α₂M dropped to half its initial concentration, no complex formation of plasmin with α₁A was demonstrated. Fibrinogen degradation products were produced by the proteolytic activity of plasmin before the enzyme became fixed to α₂M. These fragments may have influenced the clearance rate of α₂M/plasmin complexes by a competitive overload of the reticuloendothelial system. Indeed, Ohlsson [2] observed a half-life of only 8 min when bovine trypsin complexed with canine α₁M and α₂M was injected to dogs. However, in this experiment a heterologous enzyme was used and the clearance speed might have been influenced by the foreign proteins which are always quickly removed from circulation. Thus it seemed necessary to check the half-life time in plasma of such complexes obtained by the interaction of human α₂M with human enzymes. Indeed some information thus might be obtained in order to know whether preparations of injectable α₂M which are now available might constitute a useful tool during an acute proteolytic unbalance such as massive fibrinolysis. No observations were made concerning the removal from circulation of α₁antitrypsin (α₂A) and inter-α-trypsin inhibitor (ITI, protein π) proteinase complexes but the presence of “inactive” α₁ A in biological fluids has been reported. Now in contrast to α₂M these inhibitors interact with the active sites of the proteolytic enzymes forming complexes devoid of any enzymatic (esterasic) activity. Thus some preliminary experiments concerning the plasmatic clearance of α₁ A/trypsin and ITI/trypsin were included in this study.