title: Oral tolerance attenuates changes in in vitro lung tissue mechanics and extracellular matrix remodeling induced by chronic allergic inflammation in guinea pigs.
abstract: Recent studies emphasize the presence of alveolar tissue inflammation in asthma. Immunotherapy has been considered a possible therapeutic strategy for asthma, and its effect on lung tissue had not been previously investigated. Measurements of lung tissue resistance and elastance were obtained before and after both ovalbumin and acetylcholine challenges. Using morphometry, we assessed eosinophil and smooth muscle cell density, as well as collagen and elastic fiber content, in lung tissue from guinea pigs with chronic pulmonary allergic inflammation. Animals received seven inhalations of ovalbumin (1-5 mg/ml; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). The ovalbumin-exposed animals presented an increase in baseline and in postchallenge resistance and elastance related to baseline, eosinophil density, and collagen and elastic fiber content in lung tissue compared with controls. Baseline and post-ovalbumin and acetylcholine elastance and resistance, eosinophil density, and collagen and elastic fiber content were attenuated in OT1 and OT2 groups compared with the OVA group. Our results show that inducing oral tolerance attenuates lung tissue mechanics, as well as eosinophilic inflammation and extracellular matrix remodeling induced by chronic inflammation.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, São Paulo SP, Brazil.
authors.forename: Adriane S
authors.initials: AS
authors.lastname: Nakashima
authors.forename: Carla M
authors.initials: CM
authors.lastname: Prado
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lanças
authors.forename: Viviane C
authors.initials: VC
authors.lastname: Ruiz
authors.forename: David I
authors.initials: DI
authors.lastname: Kasahara
authors.forename: Edna A
authors.initials: EA
authors.lastname: Leick-Maldonado
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolhnikoff
authors.forename: Milton A
authors.initials: MA
authors.lastname: Martins
authors.forename: Iolanda F L C
authors.initials: IF
authors.lastname: Tibério
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000403:Airway Resistance; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006168:Guinea Pigs; D007108:Immune Tolerance; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008170:Lung Compliance; D010047:Ovalbumin / Q000008:administration & dosage; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors
chemical_list: D010047:Ovalbumin; D003094:Collagen