PMID- 27122021
OWN - NLM
STAT- MEDLINE
DCOM- 20170206
LR  - 20181113
IS  - 1559-0267 (Electronic)
IS  - 1080-0549 (Print)
IS  - 1080-0549 (Linking)
VI  - 51
IP  - 2
DP  - 2016 Oct
TI  - Bradykinin: Inflammatory Product of the Coagulation System.
PG  - 152-61
LID - 10.1007/s12016-016-8540-0 [doi]
AB  - 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.
FAU - Hofman, Zonne
AU  - Hofman Z
AD  - Laboratory of Clinical Chemistry and Hematology, University Medical Center 
      Utrecht, Utrecht, The Netherlands.
AD  - Laboratory of Translational Immunology, University Medical Center Utrecht, 
      Utrecht, The Netherlands.
FAU - de Maat, Steven
AU  - de Maat S
AD  - Laboratory of Clinical Chemistry and Hematology, University Medical Center 
      Utrecht, Utrecht, The Netherlands.
FAU - Hack, C Erik
AU  - Hack CE
AD  - Laboratory of Translational Immunology, University Medical Center Utrecht, 
      Utrecht, The Netherlands.
FAU - Maas, Coen
AU  - Maas C
AD  - Laboratory of Clinical Chemistry and Hematology, University Medical Center 
      Utrecht, Utrecht, The Netherlands. c.maas-4@umcutrecht.nl.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Clin Rev Allergy Immunol
JT  - Clinical reviews in allergy & immunology
JID - 9504368
RN  - 0 (Biomarkers)
RN  - 0 (Inflammation Mediators)
RN  - 9001-30-3 (Factor XII)
RN  - 9001-91-6 (Plasminogen)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Angioedema/blood/etiology/metabolism
MH  - Animals
MH  - Biomarkers
MH  - *Blood Coagulation
MH  - Bradykinin/*metabolism
MH  - Enzyme Activation
MH  - Factor XII/metabolism
MH  - Fibrinolysis
MH  - Humans
MH  - Inflammation Mediators/*metabolism
MH  - Mast Cells/immunology/metabolism
MH  - Neutrophil Activation/immunology
MH  - Neutrophils/immunology/metabolism
MH  - Plasminogen/metabolism
PMC - PMC5025506
OTO - NOTNLM
OT  - Angioedema
OT  - Bradykinin
OT  - D-dimer
OT  - Factor XII
OT  - HAE
OT  - Histamine
OT  - Plasmin
EDAT- 2016/04/29 06:00
MHDA- 2017/02/07 06:00
PMCR- 2016/04/28
CRDT- 2016/04/29 06:00
PHST- 2016/04/29 06:00 [entrez]
PHST- 2016/04/29 06:00 [pubmed]
PHST- 2017/02/07 06:00 [medline]
PHST- 2016/04/28 00:00 [pmc-release]
AID - 10.1007/s12016-016-8540-0 [pii]
AID - 8540 [pii]
AID - 10.1007/s12016-016-8540-0 [doi]
PST - ppublish
SO  - Clin Rev Allergy Immunol. 2016 Oct;51(2):152-61. doi: 10.1007/s12016-016-8540-0.