Original article
Kinin formation in hereditary angioedema plasma: evidence against kinin derivation from C2 and in support of “spontaneous” formation of bradykinin,☆☆

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Abstract

Hereditary angioedema (HAE) is due to a functional deficiency of the inhibitor of the activated first component of complement (C1 INH). This abnormality is thought to be responsible for the generation of a kininlike peptide in HAE plasma that is derived from the second component of complement (C2). Specifically, a combination of C2 cleavage by C1s and C2 fragment cleavage by plasmin has been reported to generate a kinin that is distinguishable from bradykinin. We have attempted to generate this peptide by activating the classical complement pathway by incubation of plasma with immune complexes and then adding plasmin or by incubating purified C1s with C4 and C2 and then adding either plasmin or trypsin. We performed a total of 13 experiments, and in no case was a kininlike molecule generated as assessed by contraction of the estrus rat uterus. However, incubation of EDTA-treated HAE plasma at 37 °C for time intervals up to 1 hr progressively generated a smooth muscle-contracting activity. This activity was resistant to tryptic digestion but was destroyed after incubation with carboxypeptidase B, an inhibition profile consistent with that of bradykinin. We therefore propose that bradykinin alone, or in combination with other factors heretofore unrecognized, might be responsible for the swelling that is characteristic of hereditary angioedema.

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  • Cited by (0)

    This investigation was supported by grant 5R01-HL23714-02 from the National Heart, Lung and Blood Institute and grant P50AL 16337-02 from the National Institute of Allergy and Infectious Disease.

    ☆☆

    Presented in part at the annual meetings of the AAP/ASCI/AFCR National meeting, Washington, D. C., May 1982.

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