Background: 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 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. Methods: 5d old rats were treated with carrier (control), betamethasone (intraperitoneally), recombinant human keratinocyte growth factor (rhuKGF) (subcutaneously) or their combination for 48h. Animals were intraperitoneally injected with 50mg/kg [D9-methyl]choline chloride 1.5, 3.0 and 6.0h prior to sacrifice at d7, and lung lavage fluid (LLF) and tissue harvested. Endogenous PC, D9-labeled PC species and their water-soluble precursors (D9-)choline and (D9-)phosphocholine were determined by tandem mass spectrometry. Results: 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 controls, peak D9-PC in lavaged lung was reached after 3h, and was decreased at 6h. Only 13% of this net loss in lavaged lung was found in LLF. Such decrease was also present in lungs treated with betamethasone, but not with rhuKGF alone. D9-PC loss at 3-6h and PC synthesis calculated from D9-enrichment of phosphocholine indicated that daily synthesis rate is higher than total pool size. Conclusion: Lung tissue contributes to systemic PC homeostasis in neonatal rats, which is altered by glucocorticoid and rhuKGF treatment.
- pulmonary phosphatidylcholine metabolism
- keratinocyte growth factor
- neonatal rat surfactant
- stable isotope labelling
- Copyright © 2016, American Journal of Physiology - Lung Cellular and Molecular Physiology