Coagulation factors induce human skin mast cell and basophil degranulation via activation of complement 5 and the C5a receptor

Yanase, Yuhki; Matsuo, Yoshimi; Takahagi, Shunsuke; Kawaguchi, Tomonori; Uchida, Kenzo; Ishii, Kaori; Tanaka, Akio; Matsubara, Daiki; Ozawa, Koichiro; Hide, Michihiro

doi:10.1016/j.jaci.2020.08.018

Cited by 30 publications

(34 citation statements)

References 10 publications

(21 reference statements)

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“…Moreover, the expression of PAR-2 on human mast cells is upregulated in urticarial lesions compared with non-urticarial lesions [ 28 ]. We also detected clear expression of PAR-1 and marginal expression of PAR-2 mRNA in human skin mast cells [ 29 ]. Nevertheless, we could not detect histamine release from skin mast cells in response to TRAP-6, a PAR-1 agonist, or AC55541, a PAR-2 agonist [ 29 ].…”

Section: The Role Of Protease-activated Protein (Par)mentioning

confidence: 99%

“…We also detected clear expression of PAR-1 and marginal expression of PAR-2 mRNA in human skin mast cells [ 29 ]. Nevertheless, we could not detect histamine release from skin mast cells in response to TRAP-6, a PAR-1 agonist, or AC55541, a PAR-2 agonist [ 29 ].…”

Section: The Role Of Protease-activated Protein (Par)mentioning

confidence: 99%

“…Fxa and FIIa then induced gap-formation of vascular endothelial cells via PAR-1 and leakage of plasma out of blood vessels ( Figure 2 and Figure 3) [ 31 , 32 ]. We also reported that adenosine, a metabolite of ATP, suppressed TF expression on vascular endothelial cells in response to the TF inducers, suggesting that adenosine-related molecules might be effective therapeutically for CSU [ 29 ]. Although clinical evidence on the role of TF expressed on vascular endothelial cells is still limited, further studies on the clinical roles of vascular endothelial cells would allow us to develop useful drugs and treatments for patients with severe and refractory CSU, targeting the TF-extrinsic coagulation pathway–plasma leakage axis.…”

Section: The Role Of Vascular Endothelial Cells In Csumentioning

confidence: 99%

“…Since the lifetime of basophils is as short as 3 days or less, newly differentiated basophils in the bone marrow expressing FcεRIs without IgE are exposed to a high concentration of IgE when these cells move into the blood circulation, resulting in the release of a small amount of histamine and the synergic expression of TF on vascular endothelial cells in patients with CSU [ 41 ]. Moreover, basophils express C3a receptor (C3aR) and C5aR, which are increased in CSU skin lesions, and release histamine predominantly in response to C5a [ 29 ]. Therefore, basophils may contribute to edema formation by releasing histamine in response to C5a both in the blood circulation and in the dermis.…”

Section: The Role Of Leukocytes In Csumentioning

confidence: 99%

“…Zhu et al suggested that the plasma level of C5a is increased in patients with CSU [ 15 ]. We recently demonstrated that the active forms of coagulation factors (FXa and FIIa) produce C5a from C5 ( Figure 2 and Figure 3 ) [ 29 ]. Moreover, C5a, but not C3a, induced the release of histamine from human skin mast cells and peripheral blood basophils via C5aR without antigens and IgE interaction ( Figure 3 ) [ 29 ].…”

Section: The Role Of the Complement System In Csumentioning

confidence: 99%

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The Role of Coagulation and Complement Factors for Mast Cell Activation in the Pathogenesis of Chronic Spontaneous Urticaria

Yanase

Takahagi

Ozawa

et al. 2021

Cells

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Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by an almost daily recurrence of wheal and flare with itch for more than 6 weeks, in association with the release of stored inflammatory mediators, such as histamine, from skin mast cells and/or peripheral basophils. The involvement of the extrinsic coagulation cascade triggered by tissue factor (TF) and complement factors, such as C3a and C5a, has been implied in the pathogenesis of CSU. However, it has been unclear how the TF-triggered coagulation pathway and complement factors induce the activation of skin mast cells and peripheral basophils in patients with CSU. In this review, we focus on the role of vascular endothelial cells, leukocytes, extrinsic coagulation factors and complement components on TF-induced activation of skin mast cells and peripheral basophils followed by the edema formation clinically recognized as urticaria. These findings suggest that medications targeting activated coagulation factors and/or complement components may represent new and effective treatments for patients with severe and refractory CSU.

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Section: The Role Of Protease-activated Protein (Par)mentioning

confidence: 99%

Section: The Role Of Protease-activated Protein (Par)mentioning

confidence: 99%

Section: The Role Of Vascular Endothelial Cells In Csumentioning

confidence: 99%

Section: The Role Of Leukocytes In Csumentioning

confidence: 99%

Section: The Role Of the Complement System In Csumentioning

confidence: 99%

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The Role of Coagulation and Complement Factors for Mast Cell Activation in the Pathogenesis of Chronic Spontaneous Urticaria

Yanase

Takahagi

Ozawa

et al. 2021

Cells

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Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response

Gimeno

Ribas‐Llauradó

Pesqué

et al. 2023

Clinical & Translational All

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Background Despite advances in the treatment of chronic urticaria, in a significant percentage of the patients symptoms are not fully controlled with conventional approaches. New strategies under development include blocking intracellular mediators of mast cell and basophil activation. Objective We aim to investigate the effects of the Bruton's tyrosine kinase (BTK) inhibitor remibrutinib on human blood basophils and CD34 + ‐derived mast cells activation induced by serum obtained from chronic urticaria patients. Methods Twenty‐two patients with chronic spontaneous urticaria (mean age 52 years, 27% women) and 22 patients with chronic inducible urticaria (46 years, 27% women) were included in the study together with a sex‐matched control group. Patients were classified as responders or non‐responders to anti‐IgE therapy on the basis of their clinical data, FcεR1a expression on blood basophils and total IgE levels. Changes on CD63 expression—as an activation marker‐, were used to evaluate in vitro the response of basophils and mast cells to serum exposure and the inhibitory effects of remibrutinib. Results Remibrutinib inhibits degranulation induced by IgE cross‐linking in mast cells and basophils and also the activation triggered by factors present in the sera of spontaneous and inducible chronic urticaria patients. Patient's serum induces a greater degranulation of effector cells than controls. Activation of mast cells and basophils by patient sera and remibrutinib effects were not related to omalizumab responsiveness. Conclusion Remibrutinib inhibits activation of human basophils and mast cells induced in vitro by exposure to the serum of chronic urticaria patients independently of their response to omalizumab.

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Immunopathogenesis of urticaria: a clinical perspective on histamine and cytokine involvement

Bhowmik,

Shaharyar,

Sarkar

et al. 2024

Inflamm. Res.

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Coagulation factors induce human skin mast cell and basophil degranulation via activation of complement 5 and the C5a receptor

Cited by 30 publications

References 10 publications

The Role of Coagulation and Complement Factors for Mast Cell Activation in the Pathogenesis of Chronic Spontaneous Urticaria

The Role of Coagulation and Complement Factors for Mast Cell Activation in the Pathogenesis of Chronic Spontaneous Urticaria

Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response

Immunopathogenesis of urticaria: a clinical perspective on histamine and cytokine involvement

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