Angioedema Induced by a Peptide Derived from Complement Component

Several lines of experimental evidence have suggested that one or more peptides that can enhance vascular permeability may be released from the second component ofhuman complement, C2 (1-5) . This possibility is important to understanding the molecular mechanisms that lead to bouts of circumscribed edema to which persons with hereditary angioneurotic edema (HANE)' are susceptible. Persons with this disorder have defects in the biosynthesis of Cl inhibitor, which are inherited as autosomal dominant traits and are markedly deficient in serum inhibitory activity directed against the activated first component ofcomplement, C1 (6, 7) . An acquired form of this disease, which occurs as a result of C1 inhibitor depletion, has also been reported (8-11) . The mediators of the enhanced vascular permeability that leads to edema formation when C1 inhibitor is deficient are not known. Cl activity is strictly controlled by C1 inhibitor (12), which binds covalently to the C1 complex (13-16). Since Cl inhibitor is the only identified inhibitor of Clr and Cls, the absence or depletion of this plasma component results in a loss of regulation of the early steps of the classical complement pathway. It has been shown in patients with HANE that C2 and C4 levels are low during and after an attack (1) . The present studies are a direct approach to determining if C2 fragments, which can be released by C1 and other plasma proteases inhibited by Cl inhibitor, contribute to enhanced vascular permeability andsubsequent bouts ofangioedema . We have found that a synthetic peptide of 25 residues identical in sequence to residues 199-223 of the COOH terminus of C2b has such a property.