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BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT)

We systematically examined by immune-histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 ho...

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Autores principales: Guest, Ian, Sell, Stewart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520747/
https://www.ncbi.nlm.nih.gov/pubmed/26006019
http://dx.doi.org/10.1038/labinvest.2015.72
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author Guest, Ian
Sell, Stewart
author_facet Guest, Ian
Sell, Stewart
author_sort Guest, Ian
collection PubMed
description We systematically examined by immune-histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 hours after a single challenge there is fibrinoid necrosis of arterial walls with deposition of immunoglobulin and OVA and infiltration of eosinophilic polymorphonuclear cells that lasts for about 3 days followed by peribronchial B-cell infiltration and slight reversible goblet cell hypertrophy. After 2 challenges, severe eosinophilic vasculitis is present at 6 hours, increases by 72 hours and then declines; B-cell proliferation and significant goblet cell hypertrophy and hyperplasia (GCHTH) and bronchial smooth muscle hypertrophy recur more prominently. After 3 challenges, there is significantly increased induced bronchus associated lymphoid tissue (iBALT) formation, GCHTH and smooth muscle hypertrophy. Elevated levels of Th2 cytokines: IL-4, IL-5 and IL-13, are present in bronchial lavage fluids. Sensitized mice have precipitating antibody and positive Arthus skin reactions but also develop significant levels IgE antibody to OVA but only 1 week after challenge. We conclude that the asthma like lung lesions induced in these models is preceded by immune complex mediated eosinophilic vasculitis and iBALT formation. There are elevations of Th2 cytokines that most likely produce bronchial lesions that resemble human asthma. However, it is unlikely that mast cell activated atopic mechanisms are responsible as we found only a few presumed mast cells by toluidine blue and metachromatic staining limited to the most proximal part of the main stem bronchus, and none in the remaining main stem bronchus or in the lung periphery.
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spelling pubmed-45207472016-01-31 BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT) Guest, Ian Sell, Stewart Lab Invest Article We systematically examined by immune-histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 hours after a single challenge there is fibrinoid necrosis of arterial walls with deposition of immunoglobulin and OVA and infiltration of eosinophilic polymorphonuclear cells that lasts for about 3 days followed by peribronchial B-cell infiltration and slight reversible goblet cell hypertrophy. After 2 challenges, severe eosinophilic vasculitis is present at 6 hours, increases by 72 hours and then declines; B-cell proliferation and significant goblet cell hypertrophy and hyperplasia (GCHTH) and bronchial smooth muscle hypertrophy recur more prominently. After 3 challenges, there is significantly increased induced bronchus associated lymphoid tissue (iBALT) formation, GCHTH and smooth muscle hypertrophy. Elevated levels of Th2 cytokines: IL-4, IL-5 and IL-13, are present in bronchial lavage fluids. Sensitized mice have precipitating antibody and positive Arthus skin reactions but also develop significant levels IgE antibody to OVA but only 1 week after challenge. We conclude that the asthma like lung lesions induced in these models is preceded by immune complex mediated eosinophilic vasculitis and iBALT formation. There are elevations of Th2 cytokines that most likely produce bronchial lesions that resemble human asthma. However, it is unlikely that mast cell activated atopic mechanisms are responsible as we found only a few presumed mast cells by toluidine blue and metachromatic staining limited to the most proximal part of the main stem bronchus, and none in the remaining main stem bronchus or in the lung periphery. 2015-06-01 2015-08 /pmc/articles/PMC4520747/ /pubmed/26006019 http://dx.doi.org/10.1038/labinvest.2015.72 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Guest, Ian
Sell, Stewart
BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT)
title BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT)
title_full BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT)
title_fullStr BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT)
title_full_unstemmed BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT)
title_short BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT)
title_sort bronchial lesions of mouse model of asthma are preceded by immune complex vasculitis and induced bronchial associated lymphoid tissue (ibalt)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520747/
https://www.ncbi.nlm.nih.gov/pubmed/26006019
http://dx.doi.org/10.1038/labinvest.2015.72
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