title: Meconium aspiration produces airway hyperresponsiveness and eosinophilic inflammation in a murine model.
abstract: Meconium aspiration syndrome is a cause of significant morbidity and mortality in the perinatal period and has been implicated in the pathogenesis of airway dysfunction. In this study, we developed a murine model to evaluate the effects of meconium aspiration on airway physiology and lung cellular responses. Under light anesthesia, BALB/c mice received a single intratracheal instillation of meconium or physiological saline. Respiratory mechanics were measured in unrestrained animals and expressed as percent increase in enhanced pause to increasing concentrations of methacholine (MCh). Furthermore, we assessed the changes in cells and cytokines into the bronchoalveolar lavage fluid (BALF). We found meconium aspiration produced increased airway responsiveness to MCh at 7 days. These functional changes were associated with lymphocytic/eosinophilic inflammation, goblet cell metaplasia, and increased concentrations of IL-5 and IL-13 in the BALF. Our findings suggest meconium aspiration leads to alterations of airway function, lung eosinophilia, goblet cell metaplasia, and cytokine imbalance, thus providing the first evidence of meconium-induced airway dysfunction in a mouse model.
authors.affiliation: Department of Pediatrics, University of Texas-Houston Medical School, 77030, USA.
authors.forename: Amir M
authors.initials: AM
authors.lastname: Khan
authors.forename: Okan
authors.initials: O
authors.lastname: Elidemir
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Epstein
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Lally
authors.forename: Hasen
authors.initials: H
authors.lastname: Xue
authors.forename: Michael
authors.initials: M
authors.lastname: Blackburn
authors.forename: Gary L
authors.initials: GL
authors.lastname: Larsen
authors.forename: Giuseppe N
authors.initials: GN
authors.lastname: Colasurdo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007231:Infant, Newborn; D008168:Lung / Q000276:immunology / Q000473:pathology; D008471:Meconium Aspiration Syndrome / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D015656:Respiratory Mechanics / Q000276:immunology
chemical_list: D016207:Cytokines