title: Bronchopulmonary dysplasia impairs L-type amino acid transporter-1 expression in human and baboon lung.
abstract: 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 prevent experimental and clinical BPD. Earlier studies showed that NO 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, we sought to determine whether pulmonary LAT1 expression is altered in preterm baboons with experimental BPD and in human newborns susceptible to developing BPD. Using fixed lung obtained from 125 d to 140 d gestation baboon models of BPD, LAT1 immunostaining was measured in control and BPD animals. In adult controls and in 140 d gestational controls (GC), LAT1 was expressed in both type I and type II AECs. In 140 d BPD lungs, LAT1 expression density in alveolar tissue was decreased. In 125 d GC baboons, LAT1 immunostaining was largely confined to cuboidal AECs, whereas animals given 14 d of mechanical ventilation exhibited diminished alveolar septal LAT1 Labeling. The pattern in adult human donor lung was comparable to that observed in adult baboons. LAT1 was expressed in lungs obtained from some but not all very premature newborns at autopsy. In human and baboon lung, adult and newborn, pulmonary vascular cells expressed LAT1. In summary, LAT1 is expressed in AECs and pulmonary vascular cells in baboons and humans. Experimental BPD in premature baboons decreases pulmonary LAT1 expression and alters its spatial localization. Heterogeneity of functional LAT1 could affect S-nitrosothiol importation, which could impair iNO therapy. Pediatr Pulmonol. 2016;51:1048-1056. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, 27710, North Carolina.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Bao
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, 27710, North Carolina.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Chystsiakova
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, 27710, North Carolina.
authors.forename: Mulugu V
authors.initials: MV
authors.lastname: Brahmajothi
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Sunday
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Pavlisko
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Wempe
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, 27710, North Carolina. richard.auten@conehealth.com.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Auten
mesh_terms: D000328:Adult; D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010215:Papio; D012121:Respiration, Artificial
chemical_list: D027283:Large Neutral Amino Acid-Transporter 1; D009569:Nitric Oxide; D010100:Oxygen
keywords: lung diseases; neonatology; pulmonary medicine