title: Phosphatidylcholine kinetics in neonatal rat lungs and the effects of rhuKGF and betamethasone.
abstract: Surfactant, synthesized by type II pneumocytes (PN-II), mainly comprises phosphatidylcholine (PC) and is essential to prevent neonatal respiratory distress. Furthermore, PC is essential to lung tissue growth and maintenance as a membrane component. Recent findings suggest that the lung contributes to systemic lipid homeostasis via PC export through ABC-A1 transporter expression. Hence it is important to consider pharmacological interventions in neonatal lung PC metabolism with respect to such export. Five-day-old rats were treated with carrier (control), intraperitoneal betamethasone, subcutaneous recombinant human keratinocyte growth factor (rhuKGF), or their combination for 48 h. Animals were intraperitoneally injected with 50 mg/kg [D9-methyl]choline chloride 1.5, 3.0, and 6.0 h before death at day 7, and lung lavage fluid (LLF) and tissue were harvested. Endogenous PC, D9-labeled PC species, and their water-soluble precursors (D9-)choline and (D9-)phosphocholine were determined by tandem mass spectrometry. Treatment increased secreted and tissue PC pools but did not change equilibrium composition of PC species in LLF. However, all treatments increased specific surfactant components in tissue. In control rats, peak D9-PC in lavaged lung was reached after 3 h and was decreased at 6 h. Only 13% of this net loss in lavaged lung was found in LLF. Such decrease was not present in lungs treated with betamethasone and/or with rhuKGF. D9-PC loss at 3-6 h and PC synthesis calculated from D9 enrichment of phosphocholine indicated that daily synthesis rate is higher than total pool size. We conclude that lung tissue contributes to systemic PC homeostasis in neonatal rats, which is altered by glucocorticoid and rhuKGF treatment.
authors.affiliation: Department of Neonatology, Faculty of Medicine, Eberhard-Karls-University, Tübingen, Germany; and wolfgang.bernhard@med.uni-tuebingen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bernhard
authors.affiliation: Department of Pediatric Surgery, Faculty of Medicine, Eberhard-Karls-University, Tübingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Gesche
authors.affiliation: Department of Neonatology, Faculty of Medicine, Eberhard-Karls-University, Tübingen, Germany; and.
authors.forename: Marco
authors.initials: M
authors.lastname: Raith
authors.affiliation: Department of Neonatology, Faculty of Medicine, Eberhard-Karls-University, Tübingen, Germany; and.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Poets
mesh_terms: D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D005938:Glucocorticoids; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D051523:Fibroblast Growth Factor 7; D001623:Betamethasone
keywords: betamethasone; keratinocyte growth factor; mass spectrometry; neonatal rat; phosphatidylcholine metabolism; pulmonary phospholipid turnover; stable isotope labeling; surfactant turnover