Bradykinin: Inflammatory Product of the Coagulation System

详细信息    查看全文

• 作者：Zonne Hofman ; Steven de Maat ; C. Erik Hack…
• 关键词：Angioedema ; HAE ; Histamine ; Bradykinin ; Factor XII ; Plasmin ; D ; dimer
• 刊名：Clinical Reviews in Allergy & Immunology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：51
• 期：2
• 页码：152-161
• 全文大小：1,022 KB
• 刊物主题：Allergology; Immunology; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-0267
• 卷排序：51

文摘

Episodic and recurrent local cutaneous or mucosal swelling are key features of angioedema. The vasoactive agents histamine and bradykinin are highly implicated as mediators of these swelling attacks. It is challenging to assess the contribution of bradykinin to the clinical expression of angioedema, as accurate biomarkers for the generation of this vasoactive peptide are still lacking. In this review, we will describe the mechanisms that are responsible for bradykinin production in hereditary angioedema (HAE) and the central role that the coagulation factor XII (FXII) plays in it. Evidently, several plasma parameters of coagulation change during attacks of HAE and may prove valuable biomarkers for disease activity. We propose that these changes are secondary to vascular leakage, rather than a direct consequence of FXII activation. Furthermore, biomarkers for fibrinolytic system activation (i.e. plasminogen activation) also change during attacks of HAE. These changes may reflect triggering of the bradykinin-forming mechanisms by plasmin. Finally, multiple lines of evidence suggest that neutrophil activation and mast-cell activation are functionally linked to bradykinin production. We put forward the paradigm that FXII functions as a ‘sensor molecule’ to detect conditions that require bradykinin release via crosstalk with cell-derived enzymes. Understanding the mechanisms that drive bradykinin generation may help to identify angioedema patients that have bradykinin-mediated disease and could benefit from a targeted treatment.