Angioedema induced by a peptide derived from complement component C2.

Abstract

Synthetic peptides that correspond to the COOH-terminal portion of C2b enhance vascular permeability in human and guinea pig skin. In human studies, 1 nmol of the most active peptide of 25-amino acid residues produced substantial local edema. A pentapeptide and a heptapeptide corresponding to the COOH-terminal sequence of C2b each induced contraction of estrous rat uterus in the micromole range; a peptide of 25 amino acids from this region induced a like contraction of rat uterus at a concentration 20-fold lower than the smaller peptides. The vascular permeability of guinea pig skin was enhanced by doses of these synthetic peptides in a similar fashion as that observed for the concentration of rat uterus. The induction of localized edema by intradermal injection in both the guinea pig and the human proceeds in the presence of antihistaminic drugs, suggesting that there is a histamine-independent component to the observed increase in vascular permeability. Cleavage of C2 with the enzymic subcomponent of C1, C1s, yields only C2a and C2b, and no small peptides, whereas cleavage of C2 with C1s and plasmin yields a set of small peptides. These plasmin-cleaved peptides are derived from the COOH terminus of C2b, and they induce the contraction of estrous rat uterus.

Increased vascular permeability in C1 inhibitor–deficient mice mediated by the bradykinin type 2 receptor

“…However, the pathophysiology of the increased vascular permeability of HAE has remained controversial for over 30 years. It is believed that angioedema results from uncontrolled activation of either the classical complement pathway with generation of a vasoactive peptide (C2 kinin) released from C2, and/or from contact system activation with release of bradykinin from high-molecular-weight kininogen (7)(8)(9)(10)(11). Although the majority of the available data support a role for bradykinin, the critical question is whether bradykinin alone could account for the symptoms of patients with HAE, or other mediators are also involved.…”

Pathophysiology of Hereditary Angioedema

“…It was originally proposed that complement activation may play a principle role in the pathogenesis of these symptoms, but this was later discredited. [23][24][25][26][27] It is known that minor local trauma, stress, and other events may trigger angioedema, and it is now well established that bradykinin (BK) is the principal mediator of symptoms of C1-INH deficiency.…”

C1 Inhibitor and Diagnosis of Hereditary Angioedema in Newborns

“…The disease therefore requires special attention during events commonly encountered in childhood, such as tonsillectomy, intubation of the larynx, or laryngitis. The edema is caused by extravasation of fluid through wrinkled and leaky endothelial cells in the postcapillary venules, most probably the result of excess bradykinin formation (4) and/or a peptide liberated from C2 (5,6). Conventional antiallergic therapy in the form of antihistamines, corticosteroids, or epinephrine is insufficient.…”