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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 92, No. s2, 1997, pp. 223-226
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Bioline Code: oc97192
Full paper language: English
Document type: Research Article
Document available free of charge
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Memórias do Instituto Oswaldo Cruz, Vol. 92, No. s2, 1997, pp. 223-226
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Role Of Eosinophilic Airway Inflammation In Models
E Silva, Jose R. Lapa; Ruffie, C.; Lefort, J.; Pretolani, M. & Vargaftig, B.B.
Abstract
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 alpha4 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 hvperresponsiveness (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.
Keywords
eosinophil - alpha4 integrin - Major Basic Protein - FK506
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