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Published in: Clinical and Translational Allergy 1/2015

Open Access 01-12-2015 | Research

Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model

Authors: Mayra Álvarez-Santos, Patricia Ramos-Ramírez, Fernando Gutiérrez-Aguilar, Sandra Sánchez-Hernández, Ricardo Lascurain, Raúl Olmos-Zuñiga, Rogelio Jasso-Victoria, Norma A Bobadilla, Blanca Bazan-Perkins

Published in: Clinical and Translational Allergy | Issue 1/2015

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Abstract

Background

Caveolin-1 is a fundamental signalling scaffold protein involved in contraction; however, the role of caveolin-1 in airway responsiveness remains unclear. We evaluated the relationship between caveolin-1 expression in airway smooth muscle (ASM) and antigen-induced airway responsiveness and obstruction in a guinea pig asthma model.

Methods

Airway obstruction in sensitised guinea pigs, induced by antigenic (ovalbumin) challenges administered every 10 days, was measured. Antigen-induced responsiveness to histamine and the expression of caveolin-1 and cavin 1, 2 and 3 were evaluated at the third ovalbumin challenge. The control group received saline solution instead of ovalbumin.

Results

After the first challenge, antigen exposure induced a transient airway obstruction and airway hyperresponsiveness, high levels of IL-4 and IL-5 in lung and airway globet cells proliferation at the third antigenic challenge. Caveolin-1 mRNA levels in total lung decreased in the experimental group compared with controls. Flow cytometric analysis of ASM from the experimental group showed a high number of cells expressing caveolin-1 compared with controls. This increase was confirmed by western blot. Airway obstruction and hyperresponsiveness correlated with the degree of increased caveolin-1 expression in ASM cells (P < 0.05; r = 0.69 and −0.52, respectively). The expression of cavins 1, 2 and 3 in ASM also increased in the experimental group compared to controls. Immunohistochemical findings reveal that differences in ASM caveolin-1 were not evident between groups. Nevertheless, a marked decrease in caveolin-1 and caspase 3 was observed in the pulmonary vascular smooth muscle of asthma model compared with controls. Histological analysis did not reveal differences in smooth muscles mass or subepithelial fibrosis levels in airways between groups. However, an enlargement of smooth muscle mass was observed in the pulmonary microvessels of experimental animals. This enlargement did not induce changes in pulmonary or systemic arterial pressures.

Conclusions

Our data suggest that caveolin-1 expression in ASM has a crucial role in the development of antigen-induced airway obstruction and hyperresponsiveness in a guinea pig asthma model. In addition, the asthma model in guinea pigs appears to induce a contractile smooth muscle phenotype in the airways and a proliferative smooth muscle phenotype in pulmonary vessels.
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Metadata
Title
Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model
Authors
Mayra Álvarez-Santos
Patricia Ramos-Ramírez
Fernando Gutiérrez-Aguilar
Sandra Sánchez-Hernández
Ricardo Lascurain
Raúl Olmos-Zuñiga
Rogelio Jasso-Victoria
Norma A Bobadilla
Blanca Bazan-Perkins
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Clinical and Translational Allergy / Issue 1/2015
Electronic ISSN: 2045-7022
DOI
https://doi.org/10.1186/s13601-015-0058-7

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