Inactivation of human Factor VIII by granulocyte proteases

The effect of human granulocyte proteases and related pancreatic enzymes on the procoagulant (VIII:C) and the von Wille-brand (VIIIR:WF) activities of factor VIII was investigated. VIII:C appeared to be several hundred times more sensitive towards granulocyute enzymes than VIIIR:WF. The elastase-like protease (ELP) decreased both activities of factor VIII more effectively than the chymotrypsin-like enzyme (CLP). ELP increased co-operatively the inactivating effect of CLP. In the presence of a CLP-ELP mixture in a ratio of 3:1, the rate of inactivation of VIII:C was seven times as high as that with CLP alone. Factor VIII was more resistant towards the damaging effect of pancreatic enzymes. The rate of inactivation of VIII:C was about a thousand times and that of VIIIR:WF about a hundred times lowere than those measured with the related granulocyte enzymes of the same proteolytic activity. The sensitivity of VIII:C towards proteolysis was not as pronounced with pancreatic enzymes as with granulocyte proteases. Our data suggest that, even though CLP and ELP are called "-like# enzymes, the specificity of granulocyte proteases is not identical with that of the pancreatic enzymes. The extreme sensitivity of VIII:C for granulocyte proteases may bring about blood coagulation disorders in certain pathological conditions.