Generation of bradykinin during incubation of hereditary angioedema plasma

Curd, John G.; Yelvington, M.; Burridge, Nichola A; Stimler, N P; Gérard, Catherine; Prograis, Larry J.; Cochrane, Charles G.; Müller‐Eberhard, Hans J.

doi:10.1016/0161-5890(82)90035-9

Cited by 48 publications

(8 citation statements)

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“…The pathogenesis of edema formation in the C inhibitordeficiency syndromes is not completely understood. Increased vascular permeability capable of causing edema formation has been ascribed to complement activation with release of a C2 kinin (6,7) and/or contact system activation with release of bradykinin (8)(9)(10)(11)(12). The relative degrees ofcomplement activation and contact system activation in C inhibitor-deficient patients have not been compared, primarily because of the difficulty of assessing contact system activation in plasma.…”

Section: Introductionmentioning

confidence: 99%

Demonstration of modified inactive first component of complement (C1) inhibitor in the plasmas of C1 inhibitor-deficient patients.

Zuraw¹,

Curd²

1986

J. Clin. Invest.

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The first component of complement (C1) inhibitor plays a critical role in the regulation of the classical complement pathway and the contact system, and the deficiency of C1 inhibitor protein or function is associated with recurrent angioedema. In this study we evaluated the size of the C1 inhibitor antigens present in the plasmas of C1 inhibitor-deficient patients. We found that the Cl inhibitor in the plasmas existed in three forms: high molecular weight forms in complex with proteases, native MAO-kD C1 inhibitor, and a modified inactive 94-kD form. The proportion of the total C1 inhibitor in the 94-kD form was 28% in nine hereditary angioedema patients, 92% in five acquired C1 inhibitordeficiency patients, and 1.2% in five normal controls. In vitro activation of normal plasma with kaolin, but not heat-aggregated gamma-globulin generated 94-kD C1 inhibitor from 11O-kD C1 inhibitor. Neither kaolin activation nor heat-aggregated gammaglobulin activation generated 94-kD C1 inhibitor in Hageman factor-deficient plasma. These results suggest that 94-kD C1 inhibitor is generated in vitro by activation of the contact system. The in vivo mechanism of 94-kD C1 inhibitor generation in C1 inhibitor-deficient patients is not known.

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Section: Introductionmentioning

confidence: 99%

Demonstration of modified inactive first component of complement (C1) inhibitor in the plasmas of C1 inhibitor-deficient patients.

Zuraw¹,

Curd²

1986

J. Clin. Invest.

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“…Hageman factor (HF, coagulation Factor XII)' activates plasma prekallikrein to kallikrein, which in turn cleaves higher molecular weight kininogen to produce bradykinin, a potent mediator of vascular permeability (1). Bradykinin may play a major role in the pathogenesis of hereditary angioedema (2,3). Activation of the complement system on the other hand, leads to the production of a number of biologically active peptides, such as the anaphylatoxins, C3a (4,5), C4a (6), and C5a (7).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of activation of the classical pathway of complement by Hageman factor fragment.

Ghebrehiwet¹,

Randazzo²,

Dunn³

et al. 1983

J. Clin. Invest.

185

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“…[7]. Identification of bradykinin in activated HAE plasma by amino acid sequence has not been accomplished previously, although the co-elution of kinin activity with bradykinin was reported [6], and it has been detected by radioimmunoassay [27]. The requirement for the presence of an intact contact system for the in vitro generation of both the kinin and vasopermeability activities was also demonstrated by the generation ofactivity following reconstitution ofthe factor XII-, kallikrein-and HK-and LK-deficient plasmas (each of which had normal C2 concentrations).…”

Section: Discussionmentioning

confidence: 99%

“…Evidence for contact system involvement was suggested by studies that demonstrated its activation in plasma during attacks of angioedema [ 1 4] in the fluid of suction blisters induced in HAE patients [5]. In vitro experimental evidence that suggested bradykinin generation during incubalion (at 37 C) of remission HAE plasma supports this conclusion [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Hereditary angioneurotic oedema: characterization of plasma kinin and vascular permeability-enhancing activities

Shoemaker

Schurman

Donaldson

et al. 1994

Clinical and Experimental Immunology

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SUMMARYThe mediator(s) responsible for localized enhanced vascular permeability that characterizes an exacerbation of hereditary angioneurotic oedema (HAE) is thought to be a product of either contact or complement system activation. In contrast to normal individuals, plasma from these patients generates both kinin and vascular permeability-enhancing activity following incubation at 37°C. Depletion of C1 inhibitor in both normal and C2-deficient plasma, but not in contact factor-deficient plasmas, resulted in generation ofthese activities. The kinin activity from incubated HAE plasma was susceptible to kininase inactivation and was blocked by a Bk2 receptor antagonist. Furthermore, this activity was isolated from HAE plasma; amino acid sequence analysis proved it to be bradykinin. Similarly, the vasopermeability-enhancing activity from ethanol-fractionated or boiled HAE plasma, collected during either attack or remission, co-eluted with bradykinin on reverse-phase high performance liquid chromatography (HPLC). These studies conclusively demonstrate that bradykinin is the major kinin and mediator ofenhanced vascular permeability generated during incubation of HAE plasma. The role of other bioactive products, such as the C2 kinin, at local sites of oedema formation remains to be further defined.

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Generation of bradykinin during incubation of hereditary angioedema plasma

Cited by 48 publications

References 0 publications

Demonstration of modified inactive first component of complement (C1) inhibitor in the plasmas of C1 inhibitor-deficient patients.

Demonstration of modified inactive first component of complement (C1) inhibitor in the plasmas of C1 inhibitor-deficient patients.

Mechanisms of activation of the classical pathway of complement by Hageman factor fragment.

Hereditary angioneurotic oedema: characterization of plasma kinin and vascular permeability-enhancing activities

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