Activated factor B (Bb) of the alternative pathway of complement activation cleaves and activates plasminogen.
Activated Factor B (Bb), the central serine esterase of the alternative pathway of complement activation, exhibits restricted substrate specificity in the complement system for C3 and C5. The results presented here indicate that Bb can cleave and activate plasminogen in an experimental system containing purified plasminogen and Bb; complement cellular intermediate bearing the Bb-enzyme; or cobra venom factor-stabilized Bb-enzyme (CVF,Bb). Cleavage of plasminogen by Factor Bb generated 2 disulfide-linked polypeptides with apparent m.w. of 64,000 and 25,000 to 32,000 (SDS-PAGE). Complement cellular intermediates containing the C3b, Bb-enzyme cleave 40 to 80% of 4.5 micrograms of 125I-labeled plasminogen during 30 min of incubation at 37 degrees C; native Factor B was inactive; and anti-Factor Blg inhibited by 100% the plasminogen cleavage mediated by complement cellular intermediates bearing the Bb-enzyme. Fibrinolytic activity was detected in plasminogen activator (PA) assays when purified plasminogen and 125I-labeled fibrin tubes were incubated with Bb, CVF, Bb, or complement cellular intermediates bearing the C3b,Bb-enzyme: 10 micrograms Bb released 40 to 65% of the 125I-fibrin released by 5 micrograms urokinase in 4 hr at 37 degrees C. Plasminogen activator activity of the C3b,Bb-enzyme was found to be regulated in serum. At dilutions of NHS 1:50, the PA-activity of 1.6 micrograms Bb was 100% inhibited, and at a 1:250 dilution, 50% inhibition was observed. This report describes a novel activity for the Bb-enzyme, which constitutes the C3/C5-convertase of the alternative pathway of complement activation.
D003167:Complement Activation; D011415:Complement Factor B / Q000378:metabolism / Q000494:pharmacology*; D003170:Complement Pathway, Alternative; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000494:pharmacology*; D005342:Fibrinolysis; D006801:Humans; D010960:Plasminogen Activators / Q000378:metabolism / Q000494:pharmacology*
D004792:Enzyme Precursors; D010960:Plasminogen Activators; D011415:Complement Factor B