RESUMEN
The effect of the tetrapeptide bronchogen on the structural and functional state of the bronchial epithelium and inflammatory activity in the lungs was studied in the chronic obstructive pulmonary disease (COPD) model, created in rats by a 60-day intermittent exposure to nitrogen dioxide. The cell composition and cytokine-enzyme profile of bronchoalveolar lavage fluid (BALF), the content of secretory immunoglobulin A and surfactant protein B in BALF were determined. Following the course of peptide treatment the decreased activity of neutrophilic inflammation with the normalization of cellular composition and profile of pro-inflammatory cytokines and enzymes in the bronchoalveolar space was observed. The structure of bronchial epithelium, disturbed during formation of COPD model, was restored and accompanied by restoration of its functional activity as evidenced by an increase of secretory immunoglobulin A (local immunity marker) and surfactant protein B, responsible for reducing the alveolar surface tension.
Asunto(s)
Antiinflamatorios/farmacología , Bronquios/efectos de los fármacos , Broncodilatadores/farmacología , Oligopéptidos/farmacología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Animales , Antiinflamatorios/síntesis química , Bronquios/inmunología , Bronquios/patología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Broncoconstricción/efectos de los fármacos , Broncodilatadores/síntesis química , Modelos Animales de Enfermedad , Inmunoglobulina A/biosíntesis , Masculino , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/patología , Dióxido de Nitrógeno/administración & dosificación , Oligopéptidos/síntesis química , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/patología , Proteína B Asociada a Surfactante Pulmonar/biosíntesis , Proteína B Asociada a Surfactante Pulmonar/inmunología , Ratas , Ratas Wistar , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/patologíaRESUMEN
Effect of mast cell degranulation blockade on the inflammatory response and character of the lung tissue structure-functional changes were evaluated in the chronic obstructive pulmonary disease model produced in rats by 60-day intermittent exposure to nitrogen dioxide. The membrane stabilizer sodium cromoglicate was used to blockade of mast cell degranulation. Lung tissue sections were stained with toluidine blue to identify mast cells. Bronchoalveolar lavage fluid (BALF) cytogram was determined. The levels of mast cell tryptase and chymase, proinflammatory cytokine TNF-α, surfactant protein B were measured in BALF. Suppression of mast cell degranulation prevented the release of proteases in the bronchoalveolar space and reduced activity of the inflammatory process. The influx of inflammatory cells and TNF-α concentration decreased. There was no interstitial inflammatory infiltration. Bronchoalveolar epithelium structure was recovered that is the basis of its functional usefulness. The results confirm the active involvement of mast cells in the development of the inflammatory process in obstructive pulmonary diseases and allow us to consider them as a possible therapeutic target.
Asunto(s)
Antiinflamatorios/farmacología , Degranulación de la Célula/efectos de los fármacos , Cromolin Sódico/farmacología , Mastocitos/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Degranulación de la Célula/inmunología , Quimasas/genética , Quimasas/inmunología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Masculino , Mastocitos/inmunología , Mastocitos/patología , Dióxido de Nitrógeno/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/patología , Proteína B Asociada a Surfactante Pulmonar/genética , Proteína B Asociada a Surfactante Pulmonar/inmunología , Ratas , Ratas Wistar , Triptasas/genética , Triptasas/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
A method for experimental reproduction of stages of chronic obstructive pulmonary disease formation (from acute inflammation to bronchopulmonary tissue restructuring characteristic of this disease) is presented. Lung injury and inflammation were induced by nitrogen dioxide. Hyperplasia and hypersecretion of goblet cells, squamous cell metaplasia of the ciliary epithelium, emphysema, and focal fibrosis served as the morphological substrate for the formation of bronchial obstruction. The adequacy of the model is confirmed by signs characteristic of chronic obstructive pulmonary disease: hyperexpression of CD3 lymphocytes in the bronchial wall and parenchyma, manifold increased production of TNFα and TGFß, high concentrations of circulating pathogenic immune complexes. Persistence of the structural and functional shifts throughout 6 months after exposure to nitrogen dioxide indicated a chronic course of the resultant pathological process.