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Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps

The mechanisms underlying neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly investigated. This study aimed to examine the factors that contribute to tissue neutrophilia in CRSwNP. The numbers of neutrophils and active caspase-3-positive apoptotic neutrophil...

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Autores principales: Ruan, Jian-Wen, Zhao, Jie-Fang, Li, Xue-Li, Liao, Bo, Pan, Li, Zhu, Ke-Zhang, Feng, Qi-Miao, Liu, Jin-Xin, Yu, Zi-E, Song, Jia, Wang, Hai, Liu, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718617/
https://www.ncbi.nlm.nih.gov/pubmed/34977034
http://dx.doi.org/10.3389/fcell.2021.793073
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author Ruan, Jian-Wen
Zhao, Jie-Fang
Li, Xue-Li
Liao, Bo
Pan, Li
Zhu, Ke-Zhang
Feng, Qi-Miao
Liu, Jin-Xin
Yu, Zi-E
Song, Jia
Wang, Hai
Liu, Zheng
author_facet Ruan, Jian-Wen
Zhao, Jie-Fang
Li, Xue-Li
Liao, Bo
Pan, Li
Zhu, Ke-Zhang
Feng, Qi-Miao
Liu, Jin-Xin
Yu, Zi-E
Song, Jia
Wang, Hai
Liu, Zheng
author_sort Ruan, Jian-Wen
collection PubMed
description The mechanisms underlying neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly investigated. This study aimed to examine the factors that contribute to tissue neutrophilia in CRSwNP. The numbers of neutrophils and active caspase-3-positive apoptotic neutrophils in sinonasal tissues were assessed via immunofluorescence staining. The 95th percentile of tissue neutrophil numbers in control subjects was selected as a cut-off to define neutrophil-high (Neu-high) or neutrophil-low (Neu-low) nasal polyps (NPs). The levels of 34 inflammatory mediators in sinonasal tissues were analyzed using Bio-Plex assay. Purified human peripheral blood neutrophils were incubated with nasal tissue homogenates, and the apoptotic neutrophils were assessed via flow cytometry. The cut-off for Neu-high NPs was >10 myeloperoxidase positive cells/high-power field. Compared with Neu-low NPs, Neu-high NPs had higher tissue levels of IL-1β, IL-1Ra, IL-6, IL-8, G-CSF, MCP-1, and MIP-1α, but lower levels of IL-5, IL-13, IgE, and eosinophils. Principal component and multiple correspondence analyses revealed mixed type 1, type 2, and type 3 endotypes for Neu-low NPs, and predominant type 1 and type 3 endotypes for Neu-high NPs. Neu-high NPs had lower percentages of apoptotic neutrophils than Neu-low NPs. The numbers of neutrophils and the percentages of apoptotic neutrophils correlated with G-CSF and IL-6 levels in the NPs. Tissue homogenates from Neu-high NPs, but not those from Neu-low NPs, suppressed neutrophil apoptosis in vitro, which was reversed by anti-G-CSF treatment. Tissue neutrophil numbers were associated with difficult-to-treat disease in patients with CRSwNP after surgery. We propose that G-CSF promotes neutrophilic inflammation by inhibiting neutrophil apoptosis in CRSwNP.
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spelling pubmed-87186172022-01-01 Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps Ruan, Jian-Wen Zhao, Jie-Fang Li, Xue-Li Liao, Bo Pan, Li Zhu, Ke-Zhang Feng, Qi-Miao Liu, Jin-Xin Yu, Zi-E Song, Jia Wang, Hai Liu, Zheng Front Cell Dev Biol Cell and Developmental Biology The mechanisms underlying neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly investigated. This study aimed to examine the factors that contribute to tissue neutrophilia in CRSwNP. The numbers of neutrophils and active caspase-3-positive apoptotic neutrophils in sinonasal tissues were assessed via immunofluorescence staining. The 95th percentile of tissue neutrophil numbers in control subjects was selected as a cut-off to define neutrophil-high (Neu-high) or neutrophil-low (Neu-low) nasal polyps (NPs). The levels of 34 inflammatory mediators in sinonasal tissues were analyzed using Bio-Plex assay. Purified human peripheral blood neutrophils were incubated with nasal tissue homogenates, and the apoptotic neutrophils were assessed via flow cytometry. The cut-off for Neu-high NPs was >10 myeloperoxidase positive cells/high-power field. Compared with Neu-low NPs, Neu-high NPs had higher tissue levels of IL-1β, IL-1Ra, IL-6, IL-8, G-CSF, MCP-1, and MIP-1α, but lower levels of IL-5, IL-13, IgE, and eosinophils. Principal component and multiple correspondence analyses revealed mixed type 1, type 2, and type 3 endotypes for Neu-low NPs, and predominant type 1 and type 3 endotypes for Neu-high NPs. Neu-high NPs had lower percentages of apoptotic neutrophils than Neu-low NPs. The numbers of neutrophils and the percentages of apoptotic neutrophils correlated with G-CSF and IL-6 levels in the NPs. Tissue homogenates from Neu-high NPs, but not those from Neu-low NPs, suppressed neutrophil apoptosis in vitro, which was reversed by anti-G-CSF treatment. Tissue neutrophil numbers were associated with difficult-to-treat disease in patients with CRSwNP after surgery. We propose that G-CSF promotes neutrophilic inflammation by inhibiting neutrophil apoptosis in CRSwNP. Frontiers Media S.A. 2021-12-17 /pmc/articles/PMC8718617/ /pubmed/34977034 http://dx.doi.org/10.3389/fcell.2021.793073 Text en Copyright © 2021 Ruan, Zhao, Li, Liao, Pan, Zhu, Feng, Liu, Yu, Song, Wang and Liu. 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 Cell and Developmental Biology
Ruan, Jian-Wen
Zhao, Jie-Fang
Li, Xue-Li
Liao, Bo
Pan, Li
Zhu, Ke-Zhang
Feng, Qi-Miao
Liu, Jin-Xin
Yu, Zi-E
Song, Jia
Wang, Hai
Liu, Zheng
Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps
title Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps
title_full Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps
title_fullStr Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps
title_full_unstemmed Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps
title_short Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps
title_sort characterizing the neutrophilic inflammation in chronic rhinosinusitis with nasal polyps
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718617/
https://www.ncbi.nlm.nih.gov/pubmed/34977034
http://dx.doi.org/10.3389/fcell.2021.793073
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