Meconium aspiration produces airway hyperresponsiveness and eosinophilic inflammation in a murine model.
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.
Khan
Amir M
AM
Department of Pediatrics, University of Texas-Houston Medical School, 77030, USA.
Elidemir
Okan
O
Epstein
Cynthia E
CE
Lally
Kevin P
KP
Xue
Hasen
H
Blackburn
Michael
M
Larsen
Gary L
GL
Colasurdo
Giuseppe N
GN
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
D016207:Cytokines