Bradykinin: Inflammatory Product of the Coagulation System

Hofman, Z. L. M.; Maat, Steven de; Hack, C. E.; Maas, Coen

doi:10.1007/s12016-016-8540-0

Cited by 94 publications

(101 citation statements)

References 105 publications

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“…There is a large bout of evidence demonstrating that activation of the fibrinolytic system and contact system go hand in hand. 9,18,[32][33][34][35] Moreover, mast cells are pointed out as a source of fibrinolysis via excretion of tissue plasminogen activator, fibrinogenolytic properties of bèta-tryptase 36 and expression of uPAR. 37 With this study, we could not establish a correlation between PAP levels and cHK.…”

Section: Discussionmentioning

confidence: 99%

Evidence for bradykinin release in chronic spontaneous urticaria

Hofman

Elzen

Kuijpers

et al. 2020

Clin Experimental Allergy

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Background Chronic spontaneous urticaria (CSU) is characterized by recurrent itchy weals and/or angioedema and is believed to be driven by mast cell activation. It was shown that excessive mast cell activation during anaphylaxis initiates contact activation, resulting in bradykinin release. Evidence for bradykinin release was never demonstrated in CSU. Objective To study biomarkers of bradykinin release in CSU. Methods Plasma samples of CSU patients were collected during routine visits at the outpatient clinic. Cleaved high molecular weight kininogen (cHK) was used as a biomarker for bradykinin release. cHK, factor XIIa‐C1‐inhibitor (FXIIa‐C1‐INH), kallikrein‐C1‐INH, plasmin‐antiplasmin (PAP) complexes and soluble urokinase‐type plasminogen activator receptor (suPAR) levels were determined by ELISA. Clinical data and data on tryptase levels were collected from medical records. cHK levels were compared to previously determined levels in hereditary angioedema (HAE). Results One hundred seventeen samples from 88 CSU patients and 28 samples from healthy controls were analysed. Median cHK level in CSU was 9.1% (range: 1.4%‐21.5%), significantly increased compared to healthy controls (median 6.0% range: 0%‐19.9%; P = .0005) and comparable to HAE (n = 46, median 10.3%, range 0%‐44.3%, P > .9999). cHK levels normalized in patients during disease remission (median 6.5% range 1.5%‐20.8%) but were not dependent on the presence of angioedema, acute angioedema attacks or response to antihistamines. Surprisingly, cHK levels were inversely correlated to serum tryptase (r = −0.65 P = .0137). C1‐INH complexes and suPAR levels were not elevated in patients compared to healthy controls. PAP‐complex levels in patients were elevated compared to healthy controls but there was no correlation between PAP‐complex and cHK levels. Conclusions cHK levels are elevated in symptomatic CSU patients compared to healthy controls, indicating increased bradykinin production. Increased cHK levels are not limited to patients with angioedema. Clinical relevance If elevated bradykinin generation has clinical implications in the pathology of CSU is open to debate.

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Section: Discussionmentioning

confidence: 99%

Evidence for bradykinin release in chronic spontaneous urticaria

Hofman

Elzen

Kuijpers

et al. 2020

Clin Experimental Allergy

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“…The onset can be spontaneous or secondary to trauma. The contact system and bradykinin production are heavily implicated, as HAE is often related to C1inh deficiency (48), as well as by mutations in FXII (49), and can be treated with kinin B2 receptor antagonists, C1inh reconstitution therapy, and antagonists of pKal (50). The mechanisms that underlie the attacks are currently unknown, but strikingly similar symptoms are seen in a subset of stroke patients (~5%) who undergo thrombolytic therapy (51).…”

Section: Two External Enzymes That Feed Into the Contact System Durinmentioning

confidence: 99%

Processing of Factor XII during Inflammatory Reactions

2016

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The contact system was originally identified as an obsolete part of the coagulation system, but it has been repeatedly implicated in inflammatory states, such as infection, as well as in allergic- and chronic inflammatory disease. Under these conditions, there is surprisingly little evidence that factor XII (FXII) acts as a coagulation factor, and its activity appears to be mainly directed toward activation of the kallikrein–kinin system. The contact system factors interact with pathogens as well as cells of the (innate) immune system on several levels. Among others, these cells may provide negatively charged surfaces that contribute to contact activation as well as release enzymes that feed into this system. Furthermore, cellular receptors have been identified that bind contact factors at sites of inflammation. Based on the accumulated evidence, we propose a model for enzymatic crosstalk between inflammatory cells and the plasma contact system. During these reactions, FXII is enzymatically cleaved by non-contact system enzymes. This generates unactivated FXII fragments that can subsequently be rapidly activated in the fluid phase. The resulting enzyme lacks procoagulant properties, but retains its pro-inflammatory characteristic as a prekallikrein activator.

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“…Both the anti‐angiogenic and antimelanogenetic properties are thought to contribute to the efficacy of TA in melasma. TA has been used prophylactically to prevent hereditary angio‐oedema via its ability to reduce bradykinin levels through its effect on plasminogen …”

Section: Mechanisms Of Actionmentioning

confidence: 99%

The emerging importance of tranexamic acid in dermatology

2019

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Tranexamic acid (TA) is an antifibrinolytic agent, increasingly recognized as being of utility for a wide variety of skin diseases. We review the evidence supporting the use of TA for a range of dermatological indications, including (among others) melasma, postinflammatory hyperpigmentation, urticaria, angio-oedema and haemostasis, in addition to practical considerations of its use by dermatologists.

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Bradykinin: Inflammatory Product of the Coagulation System

Cited by 94 publications

References 105 publications

Evidence for bradykinin release in chronic spontaneous urticaria

Evidence for bradykinin release in chronic spontaneous urticaria

Processing of Factor XII during Inflammatory Reactions

The emerging importance of tranexamic acid in dermatology

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