Meconium enhances the release of nitric oxide in human airway epithelial cells.
Meconium aspiration syndrome (MAS) is a cause of significant morbidity and mortality in the perinatal period. Despite the clinical relevance of MAS, its pathogenesis is poorly understood and the role played by epithelial-derived metabolites not well defined. In this study, we evaluated whether exposure to meconium affects the release of nitric oxide production in human airway epithelial cells. Monolayers of A549 cells, a transformed human epithelial cell line, were incubated with various concentrations of meconium. Control cells were incubated with serum-free medium in a similar manner. The supernatant fluid was removed at various time points and assayed for nitrite production. In selected experiments, the effects of dexamethasone (10(-6) M), L-nitroarginine methyl ester (L-NAME, 10(-6) M) and indomethacin (10(-6) M) on nitrite release were evaluated. Results were obtained in terms of pmol/mg protein and expressed as % control (mean +/- SE). We found exposure to meconium produced a significant release of nitrite from A549 cells. Dexamethasone, L-NAME and indomethacin inhibited meconium-induced release of nitrite. Our findings demonstrate meconium enhances the production of nitric oxide from A549 cells suggesting that airway epithelial cells and their metabolic products may play an important role in the pathogenesis of MAS.
Khan
Amir M
AM
Department of Pediatrics, Division of Neonatology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Lally
Kevin P
KP
Elidemir
Okan
O
Colasurdo
Guiseppe N
GN
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002461:Cell Line, Transformed; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism*; D008471:Meconium Aspiration Syndrome / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000032:analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D009573:Nitrites; D009569:Nitric Oxide; D003907:Dexamethasone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin