Granulocyte enzyme mediated degradation of human fibrinogen in plasma in vitro.

Incubation of plasma with granulocyte enzymes in the presence of kallikrein inhibitor resulted in a prolonged thrombin time of the plasma and in an increased level of fibrinogen fragments, indicating that fibrinogen was digested. In accordance with this, fibrinogen digestion products could be purified by affinity chromatography from plasma after incubation with granulocyte enzymes. The isolated products resembled early X-like fibrinogen fragments, which are produced by limited digestion of purified fibrinogen with elastase. On SDS gel electrophoresis both had no intact A alpha-chains, but apparently intact fibrinogen B beta- and gamma-chains. Also, both fragments isolated from plasma and the X-like fragments produced with purified elastase had a low anticoagulant activity. Although elastase, the main fibrinolytic enzyme of the granulocyte, was rapidly complexed with inhibitors, 10-20% of the elastase activity towards succinyl-trialanyl-paranitroanilide was detectable in plasma no matter if the mixture of granulocyte enzymes or purified elastase had been added. A possible role for the alpha 2-macroglobulin-granulocyte elastase complex in the production of the digestion products in plasma is discussed.