title: Cleavage of the second component of complement by plasma proteases: implications in hereditary C1-inhibitor deficiency.
abstract: EDTA plasma from patients with hereditary angioedema (HAE), the genetic deficiency of C1-inhibitor, when incubated at 37 degrees produces a kinin-like activity which can induce contraction of oestrus rat uterus. The second component of complement (C2) has previously been suggested to be the source of this kinin-like activity, with the implication that C2-kinin is a normal product of complement activation. Our results show that purified human C2 is cleaved rapidly to C2a and C2b when added to HAE plasma, but not normal plasma or plasma from a danazol-treated HAE patient. However, the addition to HAE plasma of C2 at 20 X normal plasma concentration had no effect on the kinin activity generated on incubation at 37 degrees. In the presence of soya bean trypsin inhibitor, the rate of C2 cleavage and products were unaltered but no kinin activity was generated. C2 was cleaved by purified C1s to C2a and C2b. Incubation of C2 with trypsin resulted in cleavage to C2a and C2b followed by more extensive cleavage of both C2a and C2b. Kallikrein cleaved C2 to C2a and C2b but plasmin had no effect on C2. In no case was kinin activity generated. When C2 was cleaved by C1s to C2a and C2b then incubated with trypsin, kallikrein, or plasmin, no kinin activity was generated: only trypsin cleaved the C2 fragments further. The results suggest that C2 is not the source of the kinin-like activity generated in hereditary angioedema plasma.
mesh_terms: D000799:Angioedema / Q000235:genetics*; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency*; D003175:Complement C2 / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005341:Fibrinolysin; D006461:Hemolysis; D006801:Humans; D007705:Kinins / Q000032:analysis; D010447:Peptide Hydrolases / Q000378:metabolism*; D011487:Protein Conformation; D013997:Time Factors; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D003174:Complement C1 Inactivator Proteins; D003175:Complement C2; D007705:Kinins; D014361:Trypsin Inhibitors; D010447:Peptide Hydrolases; D005341:Fibrinolysin