title: Phosphatidylcholine synthesis, secretion, and reutilization during differentiation of the surfactant-producing type II alveolar cell from fetal rabbit lungs.
abstract: Evidence indicates that pulmonary pool sizes of choline and related intermediates available for synthesis of phosphatidylcholine, the major component of the surfactant, change during gestation. Furthermore, recent data suggest that the type II lung cells that produce the surfactant potentially can reutilize components of this material. However, the relationship of the de novo synthetic mechanism to the secretion and reutilization of phosphatidylcholine has not been established. This is particularly true in the case of the fetal lung where, although alterations in precursor pool sizes, including choline, have been demonstrated, few or no data are available concerning how phosphatidylcholine synthesis affects or is affected by secretion and reutilization of this phospholipid by fetal type II cells. The present study was undertaken to determine the effect of availability of choline on de novo synthesis of phosphatidylcholine by isolated fetal rabbit type II cells during the differentiation process. In addition, differentiating type II alveolar cells were used to examine the hypothesis that these cells incorporate phospholipid from the extracellular environment and the quantity and/or composition of this phospholipid differently affects cellular secretion or de novo phosphatidylcholine synthesis. Assuming that the cells did not discriminate between radioactive and nonradioactive choline, elevation of extracellular choline increased the synthesis of cellular phosphatidylcholine and disaturated phosphatidylcholine in a dose-dependent manner to 0.08 mM choline. Cells induced to differentiated by exposure to fibroblast-conditioned medium synthesized more total and disaturated phosphatidylcholine at all extracellular choline concentrations. Incubation of the fetal type II cells with dipalmitoylphosphatidylcholine or 1-palmitoyl-2-oleoylphosphatidylcholine significantly depressed the incorporation of [3H]choline into cellular phosphatidylcholine after 24 or 48 h, but not necessarily at both times. Dipalmitoylphosphatidylcholine depressed the secretion of [3H]choline-labeled phosphatidylcholine after incubation for 24 h. 1-Palmitoyl-2-oleoylphosphatidylcholine stimulated the secretion of tritium-labeled phosphatidylcholine at a concentration of 25 micrograms/mL after 48 h. Comparison of the phospholipid effect by incubating the cells with 50 ng of 14C-labeled phospholipid for 24 h showed that 1-palmitoyl-2-oleoylphosphatidylcholine significantly reduced the synthesis of 3H-labeled phosphatidylcholine compared to dipalmitoylphosphatidylcholine. In contrast, 1-palmitoyl-2-oleoylphosphatidylcholine stimulated secretion of 3H-labeled phosphatidylcholine compared with the disaturated moiety. The differentiation state of the cells altered the magnitude of the cellular secretion response but not the character.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Oral Biology, University of Manitoba, Winnipeg, Canada.
authors.forename: J E
authors.initials: JE
authors.lastname: Scott
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D002794:Choline / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000196:embryology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D011817:Rabbits
chemical_list: D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; D002794:Choline; C028694:1-palmitoyl-2-oleoylphosphatidylcholine