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Airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling

BACKGROUND: Airway remodeling in patients with asthma, which leads to a decline in pulmonary function, is likely the result of repeated exacerbations often provoked by aeroallergen exposures. Aeroallegen exposure triggers a stereotypic response orchestrated by growth factor cytokines and other prote...

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Autores principales: Zhu, Yanlong, Esnault, Stephane, Ge, Ying, Jarjour, Nizar N., Brasier, Allan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117591/
https://www.ncbi.nlm.nih.gov/pubmed/35590254
http://dx.doi.org/10.1186/s12014-022-09351-3
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author Zhu, Yanlong
Esnault, Stephane
Ge, Ying
Jarjour, Nizar N.
Brasier, Allan R.
author_facet Zhu, Yanlong
Esnault, Stephane
Ge, Ying
Jarjour, Nizar N.
Brasier, Allan R.
author_sort Zhu, Yanlong
collection PubMed
description BACKGROUND: Airway remodeling in patients with asthma, which leads to a decline in pulmonary function, is likely the result of repeated exacerbations often provoked by aeroallergen exposures. Aeroallegen exposure triggers a stereotypic response orchestrated by growth factor cytokines and other protein mediators. This results in a late-phase allergic reaction characterized by vascular permeability, recruitment of activated leukocytes, and activation of structural cells of the airway. The spectrum of protein mediators and their functions are incompletely understood. METHODS: Bronchoalveolar lavage fluid (BALF) samples were obtained from 12 volunteers who exhibited robust eosinophilic recruitment following segmental bronchial provocation with allergen (SBP-Ag). We systematically identified and quantified proteins in BALF using high-performance liquid chromatography–high-resolution mass spectrometry (LC–MS/MS) followed by pathway analysis and correlations with airway physiology. RESULTS: Pairwise analysis of protein abundance in BALF pre- vs post-SBP-Ag revealed that 55 proteins were upregulated and 103 proteins were downregulated. We observed enrichment of groups of proteins mapping to hemostasis/fibrin clot, platelet activation, lipoprotein assembly, neutrophil degranulation proteins, and acute-phase inflammation-airway remodeling pathways. The abundances of F2 and Fibrinogen γ (FGG) correlated with eosinophil numbers, whereas SERPINA3 negatively correlated with change in FeNO. The coagulation proteins F2 and KNG negatively correlated with FN1 an index of airway remodeling. Interestingly, patients with lower FEV(1) showed distinct allergen-induced patterns of 8 BALF proteins, including MUC1, alarmins (HSPB1), and actin polymerization factors. CONCLUSIONS: Protein abundance of the fibrin formation cascade, platelet activation and remodeling are associated with late-phase leukocyte numbers and markers of remodeling. Patients with lower FEV(1) have distinct dynamic responses to allergen. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-022-09351-3.
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spelling pubmed-91175912022-05-19 Airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling Zhu, Yanlong Esnault, Stephane Ge, Ying Jarjour, Nizar N. Brasier, Allan R. Clin Proteomics Research BACKGROUND: Airway remodeling in patients with asthma, which leads to a decline in pulmonary function, is likely the result of repeated exacerbations often provoked by aeroallergen exposures. Aeroallegen exposure triggers a stereotypic response orchestrated by growth factor cytokines and other protein mediators. This results in a late-phase allergic reaction characterized by vascular permeability, recruitment of activated leukocytes, and activation of structural cells of the airway. The spectrum of protein mediators and their functions are incompletely understood. METHODS: Bronchoalveolar lavage fluid (BALF) samples were obtained from 12 volunteers who exhibited robust eosinophilic recruitment following segmental bronchial provocation with allergen (SBP-Ag). We systematically identified and quantified proteins in BALF using high-performance liquid chromatography–high-resolution mass spectrometry (LC–MS/MS) followed by pathway analysis and correlations with airway physiology. RESULTS: Pairwise analysis of protein abundance in BALF pre- vs post-SBP-Ag revealed that 55 proteins were upregulated and 103 proteins were downregulated. We observed enrichment of groups of proteins mapping to hemostasis/fibrin clot, platelet activation, lipoprotein assembly, neutrophil degranulation proteins, and acute-phase inflammation-airway remodeling pathways. The abundances of F2 and Fibrinogen γ (FGG) correlated with eosinophil numbers, whereas SERPINA3 negatively correlated with change in FeNO. The coagulation proteins F2 and KNG negatively correlated with FN1 an index of airway remodeling. Interestingly, patients with lower FEV(1) showed distinct allergen-induced patterns of 8 BALF proteins, including MUC1, alarmins (HSPB1), and actin polymerization factors. CONCLUSIONS: Protein abundance of the fibrin formation cascade, platelet activation and remodeling are associated with late-phase leukocyte numbers and markers of remodeling. Patients with lower FEV(1) have distinct dynamic responses to allergen. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-022-09351-3. BioMed Central 2022-05-19 /pmc/articles/PMC9117591/ /pubmed/35590254 http://dx.doi.org/10.1186/s12014-022-09351-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhu, Yanlong
Esnault, Stephane
Ge, Ying
Jarjour, Nizar N.
Brasier, Allan R.
Airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling
title Airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling
title_full Airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling
title_fullStr Airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling
title_full_unstemmed Airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling
title_short Airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling
title_sort airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117591/
https://www.ncbi.nlm.nih.gov/pubmed/35590254
http://dx.doi.org/10.1186/s12014-022-09351-3
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