The effect of homologous thrombin and fibrinogen degradation products on fibrinogen synthesis in rabbits.
The effect of intravenous infusions of purified homologous FDP and thrombin on fibrinogen synthesis was evaluated in rabbits. De novo fibrinogen production was measured by the rate of incorporation of 75SeM into circulating fibrinogen. After receiving either 100 or 200 NIH U/kg purified homologous thrombin over 1 hr, rabbits demonstrated threefold and fivefold increases in fibrinogen synthesis, respectively. A correlation between the titers of FDP-fdp and the degree of fibrinogen synthesis was evident. Prior administration of epsilon-ACA prevented the accelerated synthesis of fibrinogen induced by thrombin and inhibited the appearance of FDP-fdp in serum. epsilon-ACA did not interfere with normal fibrinogen production. Fibrinogen synthesis was assessed following infusions of FDP prepared by vitro by digestion of rabbit fibrinogen with plasmin and subsequently identified on SDS-polyacrylamide gels. Preparations which contained predominantly stage 2 intermediate (X, Y, D, and E) or stage 3 final (D and E) fragments accelerated fibrinogen synthesis, whereas those containing predominantly stage 1 fragment X did not. Prior treatment with epsilon-ACA did not alter these results. Infusion of the supernatants derived from immunoprecipitation of the FDP by either anti-rabbit fibrinogen antibody or specific anti-human D and E antibodies significantly diminished the enhanced fibrinogen synthesis induced by the unadsorbed materials. These experiments suggest that the accelerated fibrinogen synthesis induced by thrombin is mediated by FDP, with fragments D and E appearing to be the most potent.
D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D000937:Antigen-Antibody Reactions; D011232:Chemical Precipitation; D003513:Cycloheximide / Q000494:pharmacology; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D005340:Fibrinogen / Q000096:biosynthesis*; D008297:Male; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis*
D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen; D003513:Cycloheximide; D000254:Sodium-Potassium-Exchanging ATPase; D015119:Aminocaproic Acid