On the physiological role of α2-macroglobulin

Abstract

1. 1. The activity of α 2-macroglobulin bound trypsin towards a wide spectrum of synthetic and natural substrates has been investigated. Native plasma proteins tested (fibrinogen excepted) were highly resistant to α 2-macroglobulin bound trypsin whereas denatured casein, hemoglobin and fibrin were hydrolyzed at a greatly reduced rate. However, degradation in 20 h may amount to 80% of that observed with free trypsin. The proenzymes trypsinogen and chymotrypsinogen were activated rapidly by α 2-macroglobulin bound trypsin. In a period of 30 min α 2-macroglobulin bound trypsin activated about half as much zymogen as did free trypsin. The peptide hormones angiotensin and vasopressin were destroyed almost as rapidly by α 2-macroglobulin bound trypsin as by free trypsin. Hydrolysis of synthetic substrates was reduced about 20% by complexing of trypsin with α 2-macroglobulin. Interaction of α 2-macroglobulin bound trypsin with fibrinogen appeared to be biphasic, leading first to clot formation and subsequently to clot lysis. Free trypsin acted indiscriminately on fibrinogen and formed no clots. Thus, complex formation with α 2-macroglobulin narrowed the specificity of trypsin to resemble that of both thrombin and plasmin. 2. 2. Thrombin bound by α 2-macroglobulin, contrary to earlier reports, was found to retain clotting activity although at a reduced rate. This residual clotting activity of α 2-macroglobulin bound thrombin is analogous to the slow fibrinolytic activity of α 2-macroglobulin bound plasmin and may play a role in the “hemostatic balance”. 3. 3. The implications of these findings in acute pancreatitis and certain coagulopathies have been pointed out.