Clearance of human native, proteinase-complexed, and proteolytically inactivated C1-inhibitor in rats

Smet, B. de; Boer, JP de; Agterberg, J.; Rigter, G.; Wk, Bleeker; Hack, C. E.

doi:10.1182/blood.v81.1.56.bloodjournal81156

Cited by 8 publications

(15 citation statements)

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“…The plasma clearance rates of the cleaved human and guinea pig inhibitors were intermediate between their intact and complexed forms. This is in agreement with the data previously reported by de Smet et al in rats [16]. This observation is not unique to the C1INH molecule.…”

Section: Discussionsupporting

confidence: 94%

“…As outlined, many studies indicate that the ligand binding site involved in the clearance of the serpin-protease complexes resides within the inhibitor. Although the data of Mast et al indicate that the protease does not play a role with most serpin complexes, the data here and that of de Smet et al [16] suggest a possible role for protease in C1INH clearance. In the data presented here, the catabolism of complexes with different proteases clearly differed, which suggests that the proteases themselves might be involved in the clearance of the C1INH-protease complexes.…”

Section: Discussioncontrasting

confidence: 79%

“…On the other hand, the half-life for the plasma clearance of intact human C1INH in rats was significantly shorter than the half-lives of both the human and guinea pig proteins in our study (t ½ = 4 . 5 h) [16]. This discrepancy between the turnover rates of intact human C1INH in rats and guinea pigs may also be a species difference.…”

Section: Discussionmentioning

confidence: 95%

“…This synthesis was induced via SEC I. In other studies, serpinprotease complexes were cleared more rapidly from the circulation than were the intact inhibitors [6][7][8][9][10]16]. This increase in complex clearance is facilitated by the recognition of a specific domain on the inhibitors by the SEC receptors [17].…”

Section: Introductionmentioning

confidence: 99%

“…Presumably, this domain is exposed after the change in conformation that takes place during complex formation. One study analysed the catabolism of intact, cleaved and complexed human C1INH in rats, and showed a much faster clearance of the complexes than of the intact molecule [16]. The catabolic rate of the intact molecule was significantly higher than in humans.…”

Section: Introductionmentioning

confidence: 99%

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The catabolism of intact, reactive centre-cleaved and proteinase-complexed C1 inhibitor in the guinea pig

Malek

Aulak

Davis

1996

Clinical and Experimental Immunology

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SUMMARYClearance rates in the guinea pig were determined for intact guinea pig and human C1 inhibitor, the complexes of both inhibitors with human C1s,¯factor XIIa and kallikrein, and for each inhibitor cleaved at its reactive centre with trypsin. Intact human and guinea pig C1 inhibitor were cleared from the circulation more slowly (t ½ s of 9 . 7 h and 12 . 1 h and fractional catabolic rates (FCRs) of 0 . 09 and 0 . 117) than any of their cleaved or complexed forms. The reactive centre-cleaved inhibitors were cleared with half-lives of 6 . 75 h for humans and 10 . 1 h for the guinea pig. The complexes with target proteases were catabolized much more rapidly, with half-lives ranging from 3 . 08 h to 4 . 3 h. The complexes with kallikrein were cleared more slowly than those with C1s and¯factor XIIa. Complexes prepared with the guinea pig and human inhibitors were cleared at equivalent rates. The free inactivated proteases were cleared at rates similar to the equivalent complexes, except for kallikrein, which was cleared more rapidly than its complex. The fact that the complexes with different target proteases differed in their catabolism and that protease and complex catabolism were similar suggests that protease may play a direct role in clearance.

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Section: Discussionsupporting

confidence: 94%

Section: Discussioncontrasting

confidence: 79%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The catabolism of intact, reactive centre-cleaved and proteinase-complexed C1 inhibitor in the guinea pig

Malek

Aulak

Davis

1996

Clinical and Experimental Immunology

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Detection of C1 inhibitor (SERPING1/C1NH) mutations in exon 8 in patients with hereditary angioedema: evidence for 10 novel mutations

et al. 2002

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Hereditary angioedema (HAE) is caused by mutations in the C1 inhibitor gene (SERPING1, C1NH) and the result is C1 inhibitor deficiency, either in levels or function. We have searched exon 8 for mutations by direct sequencing and analyzed the rest of the exons by SSCP in 87 Spanish families affected by HAE. Out of 87 screened families, we have detected exon 8 mutations in 26. Among these, 17 different mutations were identified: 14 point mutations and 3 frameshift. Seven of the point mutations and the three frameshift were not previously reported. Mutations were: S438P; R444P; V451G; W460X; V468D; G471E; X479R; S417fsX427; I440fsX450; E429fsX450. The rest of the families presented previously reported mutations, 5 missense and two nonsense. In none of the 26 families was an additional change identified in the rest of the exons by SSCP, and, in 20 out of the 22 families with p oint mutation, we verified that the mutation did not affect a healthy relative. Seven of these families had no history of the disease, and in five of them we were able to verify that the progenitors did not have the mutation. Therefore, they were de novo mutations.

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Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond

Agostoni¹,

Aygören‐Pürsün²,

Binkley³

et al. 2004

Journal of Allergy and Clinical Immunology

598

658

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Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

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Clearance of human native, proteinase-complexed, and proteolytically inactivated C1-inhibitor in rats

Cited by 8 publications

References 0 publications

The catabolism of intact, reactive centre-cleaved and proteinase-complexed C1 inhibitor in the guinea pig

The catabolism of intact, reactive centre-cleaved and proteinase-complexed C1 inhibitor in the guinea pig

Detection of C1 inhibitor (SERPING1/C1NH) mutations in exon 8 in patients with hereditary angioedema: evidence for 10 novel mutations

Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond

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