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Current Treatment Options in Allergy

, Volume 5, Issue 4, pp 383–391 | Cite as

Role of TF-Triggered Activation of the Coagulation Cascade in the Pathogenesis of Chronic Spontaneous Urticaria

  • Yuhki Yanase
  • Shunsuke Takahagi
  • Michihiro Hide
Urticaria and Atopic Dermatitis (M Furue and T Nakahara, Section Editors)
  • 14 Downloads
Part of the following topical collections:
  1. Topical Collection on Urticaria and Atopic Dermatitis

Abstract

Purpose of Review

To overview recent understanding of the relationship between the blood coagulation cascade and chronic spontaneous urticaria (CSU).

Recent Findings

The relationship between severities of CSU and the increase of coagulation markers, and the effectiveness of anti-coagulants, such as warfarin, suggest a causative role of the blood coagulation in the pathogenesis of CSU. However, mechanisms of the initiation of blood coagulation, and the link between blood coagulation and wheal formation in urticaria, remained unclear. In blood vessels, vascular endothelial cells and eosinophils may express tissue factor (TF), which triggers the activation of extrinsic coagulation cascade. We recently revealed that histamine and TLR agonists synergistically induce TF expression by endothelial cells and produce active forms of coagulation factors, such as Xa and IIa, which may induce plasma extravasation. The exposure of skin mast cells to the exuded plasma may then induce degranulation of the skin mast cells via various receptors, releasing a massive amount of histamine, resulting in wheal formation observed in CSU.

Summary

Further elucidation of the mechanism of blood coagulation and the pathway of mast cell activation by activated coagulation factors may be a target for the development of new and more effective treatments for CSU.

Keywords

Chronic spontaneous urticaria (CSU) Tissue factor (TF) Extrinsic coagulation cascade eosinophils Endothelial cells Mast cells Eosinophils 

Abbreviations

CSU

Chronic spontaneous urticarial

CIU

Chronic idiopathic urticarial

TF

Tissue factor

PAR

Protease-activated receptor

FcεRI

High-affinity IgE receptor

HUVEC

Human umbilical vein endothelial cells

HMVEC

Human dermal microvascular endothelial cells

TLR

Toll-like receptor

LPS

Lipopolysaccharide

IL

Interleukin

LPS

Lipopolysaccharides

SP

Substance P

MRGX2

MAS-related G protein-coupled receptor member X2

NMU

Neuromedin U

MBP

Major basic protein

EPO

Eosinophil peroxidase

CRP

C-reactive protein

PAF

Platelet-activating factor

Notes

Funding Information

The study was funded by grants to Y.Y from Takeda Science Foundation 2018 and Grant-in-Aid for Scientific Research (C).

Compliance with Ethical Standards

Conflict of Interest

Yuhki Yanase declares that he has no conflict of interest. Shunsuke Takahagi declares that he has no conflict of interest. Michihiro Hide declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Yuhki Yanase
    • 1
  • Shunsuke Takahagi
    • 1
  • Michihiro Hide
    • 1
  1. 1.Department of Dermatology, Institute of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan

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