Kinin formation in hereditary angioedema plasma: evidence against kinin derivation from C2 and in support of “spontaneous” formation of bradykinin |
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Authors: | Theodore Fields Berhane Ghebrehiwet Allen P Kaplan |
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Institution: | From the Division of Allergy, Rheumatology, and Clinical Immunology, Department of Medicine, State University of New York at Stony Brook Stony Brook, N. Y. U.S.A. |
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Abstract: | Hereditary angioedema (HAE) is due to a functional deficiency of the inhibitor of the activated first component of complement ( 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 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 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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Keywords: | HAE INH Inhibitor of first component of complement EDTA Ethylenediamine tetraacetic acid EACA Epsilon-aminocaproic acid PMSF Phenylmethylsulfonyl fluoride DEAE Diethylaminoethyl SBTI Soybean trypsin inhibitor |
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