Role of eosinophilic airway inflammation in models of asthma

Eosinophils play a central role in the establishment and outcome of bronchial inflammation in asthma. Animal models of allergy are useful to answer questions related to mechanisms of allergic inflammation. We have used models of sensitized and boosted guinea pigs to investigate the nature of bronchi...

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Main Authors: José R Lapa e Silva, C Ruffié, J Lefort, M Pretolani, BB Vargaftig
Format: Article
Language:English
Published: Fundação Oswaldo Cruz (FIOCRUZ) 1997-12-01
Series:Memorias do Instituto Oswaldo Cruz
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02761997000800032
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author José R Lapa e Silva
C Ruffié
J Lefort
M Pretolani
BB Vargaftig
author_facet José R Lapa e Silva
C Ruffié
J Lefort
M Pretolani
BB Vargaftig
author_sort José R Lapa e Silva
collection DOAJ
description Eosinophils play a central role in the establishment and outcome of bronchial inflammation in asthma. Animal models of allergy are useful to answer questions related to mechanisms of allergic inflammation. We have used models of sensitized and boosted guinea pigs to investigate the nature of bronchial inflammation in allergic conditions. These animals develop marked bronchial infiltration composed mainly of CD4+ T-lymphocytes and eosinophils. Further provocation with antigen leads to degranulation of eosinophils and ulceration of the bronchial mucosa. Eosinophils are the first cells to increase in numbers in the mucosa after antigen challenge and depend on the expression of alpha 4 integrin to adhere to the vascular endothelium and transmigrate to the mucosa. Blockage of alpha4 integrin expression with specific antibody prevents not only the transmigration of eosinophils but also the development of bronchial hyperresponsiveness (BHR) to agonists in sensitized and challenged animals, clearly suggesting a role for this cell type in this altered functional state. Moreover, introduction of antibody against Major Basic Protein into the airways also prevents the development of BHR in similar model. BHR can also be suppressed by the use of FK506, an immunosuppressor that reduces in almost 100% the infiltration of eosinophils into the bronchi of allergic animals. These data support the concept that eosinophil is the most important pro-inflammatory factor in bronchial inflammation associated with allergy.
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spelling doaj.art-d028f25915b54310b405beab46f654a42023-09-03T09:14:28ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz0074-02761678-80601997-12-019222322610.1590/S0074-02761997000800032Role of eosinophilic airway inflammation in models of asthmaJosé R Lapa e SilvaC RuffiéJ LefortM PretolaniBB VargaftigEosinophils play a central role in the establishment and outcome of bronchial inflammation in asthma. Animal models of allergy are useful to answer questions related to mechanisms of allergic inflammation. We have used models of sensitized and boosted guinea pigs to investigate the nature of bronchial inflammation in allergic conditions. These animals develop marked bronchial infiltration composed mainly of CD4+ T-lymphocytes and eosinophils. Further provocation with antigen leads to degranulation of eosinophils and ulceration of the bronchial mucosa. Eosinophils are the first cells to increase in numbers in the mucosa after antigen challenge and depend on the expression of alpha 4 integrin to adhere to the vascular endothelium and transmigrate to the mucosa. Blockage of alpha4 integrin expression with specific antibody prevents not only the transmigration of eosinophils but also the development of bronchial hyperresponsiveness (BHR) to agonists in sensitized and challenged animals, clearly suggesting a role for this cell type in this altered functional state. Moreover, introduction of antibody against Major Basic Protein into the airways also prevents the development of BHR in similar model. BHR can also be suppressed by the use of FK506, an immunosuppressor that reduces in almost 100% the infiltration of eosinophils into the bronchi of allergic animals. These data support the concept that eosinophil is the most important pro-inflammatory factor in bronchial inflammation associated with allergy.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02761997000800032eosinophilalpha4 integrinMajor Basic ProteinFK506
spellingShingle José R Lapa e Silva
C Ruffié
J Lefort
M Pretolani
BB Vargaftig
Role of eosinophilic airway inflammation in models of asthma
Memorias do Instituto Oswaldo Cruz
eosinophil
alpha4 integrin
Major Basic Protein
FK506
title Role of eosinophilic airway inflammation in models of asthma
title_full Role of eosinophilic airway inflammation in models of asthma
title_fullStr Role of eosinophilic airway inflammation in models of asthma
title_full_unstemmed Role of eosinophilic airway inflammation in models of asthma
title_short Role of eosinophilic airway inflammation in models of asthma
title_sort role of eosinophilic airway inflammation in models of asthma
topic eosinophil
alpha4 integrin
Major Basic Protein
FK506
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02761997000800032
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AT jlefort roleofeosinophilicairwayinflammationinmodelsofasthma
AT mpretolani roleofeosinophilicairwayinflammationinmodelsofasthma
AT bbvargaftig roleofeosinophilicairwayinflammationinmodelsofasthma