title: Enhanced release of thromboxane A(2) after exposure of human airway epithelial cells to meconium.
abstract: 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. Epithelial cell-derived prostanoids are involved in the regulation of several cellular functions within the lung, including the control of tone and reactivity of airway and vascular smooth muscle. In this study, we evaluated whether exposure to meconium affects the metabolic function of 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 thromboxane A(2) (TXA(2)) production. The latter was accomplished by measuring its immediate and stable metabolite thromboxane B(2), using an enzyme-linked immunosorbent assay (ELISA). In selected experiments, the modulatory effects of indomethacin (10(-6) M), dexamethasone (10(-6) M), and L-nitroarginine methyl ester (L-NAME, 10(-6) M) on TXA(2) production were evaluated. Results were expressed in terms of pg/mg protein (mean +/- SE). We found that exposure to meconium produced a significant release of TXA(2) from A549 cells. Indomethacin, dexamethasone, and in part, L-NAME inhibited meconium-induced release of TXA(2). Our findings demonstrate that meconium enhances the production of thromboxanes from A549 cells, suggesting that airway epithelial cells and their metabolic products may play an important role in the pathogenesis of MAS.
authors.affiliation: Department of Pediatrics, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
authors.forename: Amir M
authors.initials: AM
authors.lastname: Khan
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Lally
authors.forename: Gary L
authors.initials: GL
authors.lastname: Larsen
authors.forename: Giuseppe N
authors.initials: GN
authors.lastname: Colasurdo
mesh_terms: D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007231:Infant, Newborn; D008175:Lung Neoplasms / Q000378:metabolism*; D008470:Meconium; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: D013928:Thromboxane A2; D003907:Dexamethasone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin