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Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab

BACKGROUND: Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extr...

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Autores principales: Roth, Michael, Zhao, Feng, Zhong, Jun, Lardinois, Didier, Tamm, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557956/
https://www.ncbi.nlm.nih.gov/pubmed/26332463
http://dx.doi.org/10.1371/journal.pone.0136549
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author Roth, Michael
Zhao, Feng
Zhong, Jun
Lardinois, Didier
Tamm, Michael
author_facet Roth, Michael
Zhao, Feng
Zhong, Jun
Lardinois, Didier
Tamm, Michael
author_sort Roth, Michael
collection PubMed
description BACKGROUND: Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix. OBJECTIVE: We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies. METHODS: Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days. RESULTS: Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects. CONCLUSION AND CLINICAL RELEVANCE: Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC.
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spelling pubmed-45579562015-09-10 Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab Roth, Michael Zhao, Feng Zhong, Jun Lardinois, Didier Tamm, Michael PLoS One Research Article BACKGROUND: Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix. OBJECTIVE: We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies. METHODS: Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days. RESULTS: Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects. CONCLUSION AND CLINICAL RELEVANCE: Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC. Public Library of Science 2015-09-02 /pmc/articles/PMC4557956/ /pubmed/26332463 http://dx.doi.org/10.1371/journal.pone.0136549 Text en © 2015 Roth et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Roth, Michael
Zhao, Feng
Zhong, Jun
Lardinois, Didier
Tamm, Michael
Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab
title Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab
title_full Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab
title_fullStr Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab
title_full_unstemmed Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab
title_short Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab
title_sort serum ige induced airway smooth muscle cell remodeling is independent of allergens and is prevented by omalizumab
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557956/
https://www.ncbi.nlm.nih.gov/pubmed/26332463
http://dx.doi.org/10.1371/journal.pone.0136549
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