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.
Highlights
From the Lord and Taylor Laboratoryfor Lung Biochemistry, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206 and the §Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado80262
The alveolar type I1 cell of the lung produces pulmonary surfactant, a complex mixture of lipids and proteins that is secreted into the alveolar space and functions to fatty acids of 14, 16, or 18 carbons, exhibit inhibition reduce surface tension at the air-liquid interface [1].Several of surfactant secretion that correlates extremely wellof the protein components that are secreted by type I1 cells with the phase transition temperat(uTrce)of the phos- have beenidentified and these aredenoted SP’
The analysis reveals that indicates that disaturated PCs inhibit [3H]PC secretioinn a the inhibitory activity of disaturatedphosphatidylcholines Tc-dependent manner, and suggests that type I1 cells recogincreases with increasing Tc
Summary
Adherent cells and unincorporated radiolabel were removed by vigorous washing with 10 ml of DMEM containing 10 mM Hepes (pH 7.4) and 1 mg/ml bovine serumalbumin. Treatment of cultures of chromaffin cells with DPPC was without effect upon nicotine-induced secretion of [3H]norepinephrine from these cells This finding demonstrates that theinteraction of DPPC with alveolar type I1 cells is specific and probably involves a unique system present in the lung cells for interacting with extracellular lipid. Both stereoisomers were effective as inhibitors of ATP-induced surfactant secretion from isolated type I1 cells. To furtherevaluate the components of lipid structure that affect surfactant secretion, the action of dipalmitoylphosphatidyl(N-monomethyl)ethanolamine, dipalmitoylphosphatidyl(N,N-dimethyl)ethanolamine,and dipalmitoylphosphatidylcholine upon this process was compared
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