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Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli

Urticaria is characterized by the occurrence of wheals and flares in response to vasoactive mediators, such as histamine. Various studies have suggested the involvement of basophils in the pathogenesis of chronic spontaneous urticaria (CSU). However, histamine release from peripheral basophils in re...

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Autores principales: Matsubara, Daiki, Yanase, Yuhki, Ishii, Kaori, Takahagi, Shunsuke, Tanaka, Akio, Ozawa, Koichiro, Hide, Michihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559203/
https://www.ncbi.nlm.nih.gov/pubmed/36248902
http://dx.doi.org/10.3389/fimmu.2022.994823
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author Matsubara, Daiki
Yanase, Yuhki
Ishii, Kaori
Takahagi, Shunsuke
Tanaka, Akio
Ozawa, Koichiro
Hide, Michihiro
author_facet Matsubara, Daiki
Yanase, Yuhki
Ishii, Kaori
Takahagi, Shunsuke
Tanaka, Akio
Ozawa, Koichiro
Hide, Michihiro
author_sort Matsubara, Daiki
collection PubMed
description Urticaria is characterized by the occurrence of wheals and flares in response to vasoactive mediators, such as histamine. Various studies have suggested the involvement of basophils in the pathogenesis of chronic spontaneous urticaria (CSU). However, histamine release from peripheral basophils in response to stimuli acting on the high affinity IgE receptor (FcϵRI) is impaired in many patients with CSU (non/low responders). We previously demonstrated that tissue factor (TF)s expressed on vascular endothelial cells in response to a combination of various stimuli, such as that of histamine and lipopolysaccharide (LPS), activates the extrinsic coagulation pathway and produces anaphylatoxin, complement 5a (C5a), which then activates basophils and mast cells via the C5a receptor (C5aR). We have revealed that histamine release was induced in response to C5a and formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), regardless of the response to anti-IgE antibody, the reduced numbers of basophils and severity of urticaria. Moreover, we found that spontaneous release of histamine ex vivo from basophils of patients with CSU is higher than that from healthy individuals. These results suggest that basophils and the complement system, which could be activated by coagulation factors, may play a critical role in the pathogenesis of CSU, especially in cases refractory to treatment involving the IgE/FcϵRI pathway.
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spelling pubmed-95592032022-10-14 Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli Matsubara, Daiki Yanase, Yuhki Ishii, Kaori Takahagi, Shunsuke Tanaka, Akio Ozawa, Koichiro Hide, Michihiro Front Immunol Immunology Urticaria is characterized by the occurrence of wheals and flares in response to vasoactive mediators, such as histamine. Various studies have suggested the involvement of basophils in the pathogenesis of chronic spontaneous urticaria (CSU). However, histamine release from peripheral basophils in response to stimuli acting on the high affinity IgE receptor (FcϵRI) is impaired in many patients with CSU (non/low responders). We previously demonstrated that tissue factor (TF)s expressed on vascular endothelial cells in response to a combination of various stimuli, such as that of histamine and lipopolysaccharide (LPS), activates the extrinsic coagulation pathway and produces anaphylatoxin, complement 5a (C5a), which then activates basophils and mast cells via the C5a receptor (C5aR). We have revealed that histamine release was induced in response to C5a and formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), regardless of the response to anti-IgE antibody, the reduced numbers of basophils and severity of urticaria. Moreover, we found that spontaneous release of histamine ex vivo from basophils of patients with CSU is higher than that from healthy individuals. These results suggest that basophils and the complement system, which could be activated by coagulation factors, may play a critical role in the pathogenesis of CSU, especially in cases refractory to treatment involving the IgE/FcϵRI pathway. Frontiers Media S.A. 2022-09-28 /pmc/articles/PMC9559203/ /pubmed/36248902 http://dx.doi.org/10.3389/fimmu.2022.994823 Text en Copyright © 2022 Matsubara, Yanase, Ishii, Takahagi, Tanaka, Ozawa and Hide https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Matsubara, Daiki
Yanase, Yuhki
Ishii, Kaori
Takahagi, Shunsuke
Tanaka, Akio
Ozawa, Koichiro
Hide, Michihiro
Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli
title Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli
title_full Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli
title_fullStr Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli
title_full_unstemmed Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli
title_short Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli
title_sort basophils activation of patients with chronic spontaneous urticaria in response to c5a despite failure to respond to ige-mediated stimuli
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559203/
https://www.ncbi.nlm.nih.gov/pubmed/36248902
http://dx.doi.org/10.3389/fimmu.2022.994823
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