A B S T R A C T We investigated the effect of elastaselike neutral protease isolated from human granulocytes on human fibrinogen. Dependent on enzyme concentration and time of incubation, the elastase-like protease induced a progressive degradation of fibrinogen. Analysis of the remaining polypeptide chains showed a high susceptibility of the Aa-and low susceptibility of the y-chain of fibrinogen towards the proteolytic action of the enzyme. The split products were characterized by polyacrylamide gel electrophoresis and two-dimensional immunoelectrophoresis. They showed antigenic determinants of fibrinogen and of plasmin-induced proteolysis products D and E. The cleavage fragments isolated by gel chromatography had distinct molecular weights. Coagulability of fibrinogen by thrombin was inhibited according to the concentration of the protease and the time of incubation. Split products of fibrinogen with higher molecular weight prolonged the coagulation time of native fibrinogen, whereas low molecular weight fragments were ineffective.
The activity of migration inhibitory factor (MIF), present in the supernatants of specifically and nonspecifically stimulated human lymphocyte cultures, can be blocked by antiproteases of animal and plant origin and by diisopropyl fluorophosphate. MIF, partially purified by column chromatography and zone electrophoresis on polyvinylchloride is blocked in the same way. On the other hand, migration inhibition can be effected by some proteases, especially by cobra venom. These findings are discussed in terms of the probable protease nature of MIF.
The effect on human IgG of the elastase-like (ELP) and chymotrypsin-like (CLP) neutral proteases derived from human polymorphonuclear leukocytes was studied. By incubating ELP with monoclonal IgG proteins, two immunochemically and electrophoretically distinct components were formed which were similar, but not identical, to the Fc and Fab fragments produced by papain digestion. When an IgG protein was incubated under similar conditions with CLP enzyme, no proteolysis was observed. IgG proteins differed in their susceptibility to proteolysis by ELP. These differences were related to the subclasses IgG1-IgG4. The IgG1 and IgG3 proteins were readily cleaved by ELP, but the IgG2 and IgG4 proteins were more resistant. Although free light chains differ in susceptibility to proteolysis by ELP, our studies showed that neither the type (kappa or lambda) nor the subgroup of light chain affected the susceptibility of complete IgG molecules to cleavage by this enzyme.
In patients with acute severe hepatic failure the synthesis of clotting factors and inhibitors is considerably diminished. The decrease of clotting factors may be enhanced by liberation of thromboplastic substances from liver cell debris, leading to thrombus formation in the sinusoids and to further cell damage. At the low levels of clotting factors and inhibitors signs of disseminated intravascular coagulation as well as hyperfibrinolysis have been demonstrated. Treatment with heparin to prevent coagulation is insufficient at low levels of antithrombin III (AT III). Therefore, Vogel und Fritsche 1979 suggested the substitution of AT III in these cases.We now report about 3 patients who were admitted to the clinic together with severe signs of liver damage after oral uptake of CCl4
On the day of admission several clotting factors plasminogen and alpha2-antiplasmin were significantly diminished; AT III levels between 25-45% of the norm were found. (Diss. Eckhardt-Klaßnitz). Therefore we started treatment with AT III concentrate from Behringwerke (1000-2000 I.U. daily for 3 to 14 days) and fresh frozen plasma (total volume of 2 1 within the first 3 days).AT III was simultaneously determined by clotting test, a chromogenic substrate test, and immunologically. Hemodialysis was necessary in 2 patients. Unter treatment with AT III and fresh frozen plasma no bleeding tendency occured Though two of the patients showed severe intoxication on admission all could be dismissed with only slight histological signs of liver alterations. Treatment with AT III concentrates, therefore, seems of value in patients with acute yellow liver dystrophy.
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