Bronchopulmonary Dysplasia Impairs L-type Amino Acid Transporter-1 Expression in Human & Baboon Lung

Auten, Richard

Bao, Erik

2016-05-10T22:38:21Z

2016-05-10T22:38:21Z

2016-05

Biology

Bronchopulmonary dysplasia (BPD) is an inflammatory lung disorder common in premature infants who undergo mechanical ventilation with supplemental oxygen. Inhaled nitric oxide (iNO) has been used to treat BPD, but clinical outcomes in preterm newborns have been equivocal. Previous studies showed that iNO’s effects in alveolar epithelial cells (AEC) are mediated by S-nitrosothiol uptake via L-type amino acid transporter-1 (LAT1). Because LAT1 expression could influence the efficacy of iNO therapy, I sought to determine whether pulmonary LAT1 expression is altered in preterm baboons with experimental BPD and human newborns susceptible to developing BPD. Using fixed lung obtained from 125d and 140d gestation baboons, LAT1 immunostaining was measured in control vs. BPD animals. In adult and gestational controls, LAT1 was strongly expressed in AECs. In 140d BPD lungs, however, LAT1 expression density in alveolar epithelial tissue was significantly decreased. In 125d BPD lungs, LAT1 expression was also significantly diminished in AECs and was instead ectopically localized to interstitial lung regions. The pattern of LAT1 expression in adult human lung was comparable to that observed in adult baboons. LAT1 expression was comparatively diminished in the lungs of premature newborns at autopsy. In human and baboon lung, pulmonary vascular cells expressed LAT1. In summary, LAT1 is expressed in AECs and pulmonary vascular cells in baboons and humans, and BPD pathophysiology decreases pulmonary LAT1 expression and alters its spatial localization. These results could explain the current ineffectiveness of iNO therapy in premature newborns with BPD, as well as guide future work on optimizing NO-based therapies.

https://hdl.handle.net/10161/11997

en_US

Lung disease

Pediatrics

Nitric oxide

L-type amino acid transporter-1

Bronchopulmonary dysplasia

Bronchopulmonary Dysplasia Impairs L-type Amino Acid Transporter-1 Expression in Human & Baboon Lung

Honors thesis