title: Pulmonary surfactant secretion is regulated by the physical state of extracellular phosphatidylcholine.
abstract: Pulmonary alveolar type II cells synthesize, secrete, and recycle the components of pulmonary surfactant. In this report we present evidence that dipalmitoylphosphatidylcholine is a potent inhibitor of surfactant lipid secretion by type II cells. Monoenoic and dienoic phosphatidylcholines with fatty acids of 16 or 18 carbons are ineffective as inhibitors of surfactant lipid secretion. In contrast, disaturated phosphatidylcholines, with either symmetric or asymmetric pairs of fatty acids of 14, 16, or 18 carbons, exhibit inhibition of surfactant secretion that correlates extremely well with the phase transition temperature (Tc) of the phospholipid. The inhibitory activity of dipalmitoylphosphatidylcholine is not dependent upon lipid stereochemistry. N-Methylated derivatives of dipalmitoylphosphatidylethanolamine are significantly less effective than phosphatidylcholine as inhibitors. Phosphatidylcholines below their phase transition temperature are inhibitors of surfactant secretion, whereas those above their phase transition temperature are either ineffective or weakly inhibitory. The phase transition dependence of inhibition is observed when type II cells are incubated at 37 degrees C with different species of phosphatidylcholine. In addition, if type II cells are stimulated to secrete at different temperatures the efficacy of a given phospholipid as an inhibitor is dependent on its relationship to Tc (i.e. dipalmitoylphosphatidylcholine with a Tc of 41 degrees C significantly inhibits secretion at 37 degrees C but not at 42 degrees C). Inhibition of surfactant secretion by dipalmitoylphosphatidylcholine is abrogated when it is incorporated into the same liposome with dioleoylphosphatidylcholine as a 50:50 mixture. In contrast, the simultaneous addition of two separate populations of liposomes, one composed of dipalmitoylphosphatidylcholine and the other composed of dioleoylphosphatidylcholine, does not significantly alter the inhibitory activity found with dipalmitoylphosphatidylcholine alone. These data provide compelling evidence that the physical state of phosphatidylcholine can regulate surfactant secretion from alveolar type II cells and suggest a unique mechanism for regulating exocytosis in the alveolus of the lung.
authors.affiliation: Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
authors.forename: A
authors.initials: A
authors.lastname: Suwabe
authors.forename: R J
authors.initials: RJ
authors.lastname: Mason
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: J A
authors.initials: JA
authors.lastname: Firestone
authors.forename: M D
authors.initials: MD
authors.lastname: Browning
authors.forename: D R
authors.initials: DR
authors.lastname: Voelker
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000502:physiology; D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000378:metabolism; D005089:Exocytosis; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
chemical_list: D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; D009638:Norepinephrine