Human kininogens of low and high molecular mass: quantification by radioimmunoassay and determination of reference values.

Adam, Albert; Albert, Adelin; Calay, G; Closset, Jean; Damas, Jacques; Franchimont, P

doi:10.1093/clinchem/31.3.423

Cited by 42 publications

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“…In contrast, N-HK concentration values were influenced by experimental conditions. This could partially account for the discrepancy between the N-HK concentrations reported here and the 70–90μg/mL or 69–116μg/mL ranges of total plasma HK reported in previous studies ([ 41 ] and [ 42 ], respectively). The amount of cleaved HK proteins (in healthy plasma or, probably, in the standard used) might also partly explain the differences.…”

Section: Discussioncontrasting

confidence: 97%

Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions

et al. 2016

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BackgroundAngioedema without wheals (AE) is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh), but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases.ObjectivesWe wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker.MethodsWe retrospectively investigated high molecular weight kininogen (HK) cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis.ResultsCirculating native HK plasma concentrations were similar in the healthy men (interquartile range: 98–175μg/mL, n = 51) and in healthy women (90–176μg/mL, n = 74), while HK cleavage was lower (p<0.001) in men (0–5%) than women (3–9%). Patients exhibited lower native HK concentration (p<10−4; 21–117μg/mL, n = 31 for men; 0–84μg/mL, n = 41 for women) and higher HK cleavage (p<10−4; 10–30% and 14–89%, respectively) than healthy donors. Pathological thresholds were set at: <72μg/mL native HK, >14.4% HK cleavage for men; <38μg/mL; native HK, >33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13) or two weeks after AE attack (n = 2), HK cleavage was not fully restored, suggesting its use as a post-attack assay.ConclusionAs a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management.

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Section: Discussioncontrasting

confidence: 97%

Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions

et al. 2016

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“…After 10 min of equilibration, 5 ml of arterial blood was sampled in a polyethylene tube containing buffered sodium citrate (final concentration 13 m M ) for the measurement of blood kininogen reserve. These sampling procedures have been previously validated and do not result in significant kininogen consumption in vitro ( Adam et al ., 1985a , 1985b , 1985c ). The intravenous injection of test drugs used to induce B 1 Rs, dextran sulphate (2 mg kg −1 ) or LPS (50 μg kg −1 ) was then performed, and the blood sampling was repeated after 90 min in order to document acute treatment‐induced kininogen consumption.…”

Section: Methodsmentioning

confidence: 99%

Absence of ligand‐induced regulation of kinin receptor expression in the rabbit

Sabourin

Guay

Houle

et al. 2001

British J Pharmacology

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1 The induction of B 1 receptors (B 1 Rs) and desensitization or down-regulation of B 2 receptors (B 2 Rs) as a consequence of the production of endogenous kinins has been termed the autoregulation hypothesis. The latter was investigated using two models based on the rabbit: kinin stimulation of cultured vascular smooth muscle cells (SMCs) and in vivo contact system activation (dextran sulphate intravenous injection, 2 mg kg -BK binding or mRNA concentration evaluated by RT ± PCR; 4 or 3 h, respectively). Treatment with B 1 R or B 2 R agonists failed to alter B 1 R expression under the same conditions. 3 Despite consuming endogenous kininogen (assessed using the kinetics of immunoreactive kinin formation in the plasma exposed to glass beads ex vivo) and producing hypotension mediated by B 2 Rs in anaesthetized rabbits, dextran sulphate treatment failed to induce B 1 Rs in conscious animals (RT ± PCR in several organs, aortic contractility). By contrast, lipopolysaccharide (LPS, 50 mg kg 71 , 5 h) was an eective B 1 R inducer (kidney, duodenum, aorta) but did not reduce kininogen reserve. 4 We tested the alternate hypothesis that endogenous kinin participate in LPS induction of B 1 Rs. Kinin receptor antagonists (icatibant combined to B-9858, 50 mg kg 71 of each) failed to prevent or reduce the eect of LPS on B 1 R expression. Dextran sulphate or LPS treatments did not persistently down-regulate vascular B 2 Rs (jugular vein contractility assessed ex vivo). 5 The kinin receptor autoregulation hypothesis is not applicable to primary cell cultures derived from a tissue known to express B 1 Rs in a regulated manner (aorta). The activation of the endogenous kallikrein-kinin system is ineective to induce B 1 Rs in vivo in an experimental time frame sucient for B 1 R induction by LPS.

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“…In its intact form, the protein is a cysteine proteinase inhibitor, implicated in blood coagulation and inflammatory response and it can bind calcium, while the individual subchains can have many other functions [ 329 – 332 ]. Kininogen is mainly synthetized in the liver to plasma concentrations of 55–100 μg/mL, where it is mostly found in complex with prekallikrein or factor XI to position the coagulation factors near factor XII [ 331 , 333 – 336 ].…”

Section: Kininogen-1 (P01042)mentioning

confidence: 99%

Human plasma protein N-glycosylation

et al. 2015

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Glycosylation is the most abundant and complex protein modification, and can have a profound structural and functional effect on the conjugate. The oligosaccharide fraction is recognized to be involved in multiple biological processes, and to affect proteins physical properties, and has consequentially been labeled a critical quality attribute of biopharmaceuticals. Additionally, due to recent advances in analytical methods and analysis software, glycosylation is targeted in the search for disease biomarkers for early diagnosis and patient stratification. Biofluids such as saliva, serum or plasma are of great use in this regard, as they are easily accessible and can provide relevant glycosylation information. Thus, as the assessment of protein glycosylation is becoming a major element in clinical and biopharmaceutical research, this review aims to convey the current state of knowledge on the N-glycosylation of the major plasma glycoproteins alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein, alpha-2-macroglobulin, antithrombin-III, apolipoprotein B-100, apolipoprotein D, apolipoprotein F, beta-2-glycoprotein 1, ceruloplasmin, fibrinogen, immunoglobulin (Ig) A, IgG, IgM, haptoglobin, hemopexin, histidine-rich glycoprotein, kininogen-1, serotransferrin, vitronectin, and zinc-alpha-2-glycoprotein. In addition, the less abundant immunoglobulins D and E are included because of their major relevance in immunology and biopharmaceutical research. Where available, the glycosylation is described in a site-specific manner. In the discussion, we put the glycosylation of individual proteins into perspective and speculate how the individual proteins may contribute to a total plasma N-glycosylation profile determined at the released glycan level.Electronic supplementary materialThe online version of this article (doi:10.1007/s10719-015-9626-2) contains supplementary material, which is available to authorized users.

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Human kininogens of low and high molecular mass: quantification by radioimmunoassay and determination of reference values.

Cited by 42 publications

References 0 publications

Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions

Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions

Absence of ligand‐induced regulation of kinin receptor expression in the rabbit

Human plasma protein N-glycosylation

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