title: Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model.
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.
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Departamento de Hiperreactividad Bronquial, Calzada de Tlalpan, 4502 Mexico.
authors.forename: Mayra
authors.initials: M
authors.lastname: Álvarez-Santos
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Departamento de Hiperreactividad Bronquial, Calzada de Tlalpan, 4502 Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ramos-Ramírez
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Departamento de Hiperreactividad Bronquial, Calzada de Tlalpan, 4502 Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gutiérrez-Aguilar
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Departamento de Hiperreactividad Bronquial, Calzada de Tlalpan, 4502 Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sánchez-Hernández
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lascurain
authors.affiliation: Departamento de Cirugía Experimental, Instituto Nacional de Enfermedades,Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan, 4502 Mexico.
authors.forename: Raúl
authors.initials: R
authors.lastname: Olmos-Zuñiga
authors.affiliation: Departamento de Cirugía Experimental, Instituto Nacional de Enfermedades,Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan, 4502 Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Jasso-Victoria
authors.affiliation: Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, Mexico ; Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Department of Nephrology, México, Mexico.
authors.forename: Norma A
authors.initials: NA
authors.lastname: Bobadilla
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Departamento de Hiperreactividad Bronquial, Calzada de Tlalpan, 4502 Mexico.
authors.forename: Blanca
authors.initials: B
authors.lastname: Bazan-Perkins
keywords: Airway hyperresponsiveness; Airway obstruction; Airway smooth muscle; Asthma; Caveolin-1; Cavin; Pulmonary arterial smooth muscle; caspase 3