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Meconium aspiration produces airway hyperresponsiveness and eosinophilic inflammation in a murine model
Amir M Khan1, Okan Elidemir, Cynthia E Epstein
1Department of Pediatrics, University of Texas-Houston Medical School, 77030, USA.
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.
Insights
Meconium aspiration in mice causes lasting airway dysfunction and inflammation. This study reveals how meconium impacts lung health, offering insights into airway hyperresponsiveness.
Area of Science:
- Pulmonary Medicine
- Neonatal Research
- Immunology
Background:
- Meconium aspiration syndrome (MAS) is a major cause of newborn illness and death.
- MAS is linked to long-term breathing problems.
Purpose of the Study:
- To investigate the effects of meconium aspiration on lung function and cellular responses in a mouse model.
- To establish a preclinical model for studying MAS-induced airway dysfunction.
Main Methods:
- Mice received intratracheal meconium or saline under anesthesia.
- Respiratory mechanics were assessed using methacholine challenges.
- Bronchoalveolar lavage fluid (BALF) was analyzed for cells and cytokines.
Main Results:
- Meconium aspiration led to increased airway hyperresponsiveness to methacholine at 7 days post-instillation.
- Significant lymphocytic/eosinophilic inflammation and goblet cell metaplasia were observed.
- Elevated levels of IL-5 and IL-13 were detected in BALF.
Conclusions:
- Meconium aspiration induces persistent airway dysfunction in mice.
- The study demonstrates meconium-induced lung inflammation, cellular changes, and cytokine imbalance.
- This model provides evidence for meconium-induced airway dysfunction, relevant to neonatal respiratory health.