SEQUENTIAL-CHANGES IN PHOSPHOLIPID COMPOSITION AND SYNTHESIS IN LUNGS EXPOSED TO NITROGEN-DIOXIDE

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Abstract
Studies were performed to investigate the time course of biochemical and histologic changes in the lungs of rats after exposure to various concentrations of NO2. Special attention was given to identify lipid classes and the molecular species preferentially affected. Increased incorporation of thymidine, labeled with 3H, into DNA was 1st detected 12 h after a 5 h exposure to 40 ppm of NO2 and reached a peak after 24 to 36 h. The 1st histologic signs of a hyperplastic response in the alveolar ducts and alveoli became recognizable at 24 h. Increased incorporation of palmitic acid, labeled with 14C, into phosphatidylcholine and the accumulation of this lipid class in the lungs could be detected as early as 6 h after exposure to NO2. Lung wet weights and lung protein were also increased at this time. The increase in phosphatidylcholine in the lungs exposed to NO2 may occur before commencement of the regenerative hyperplastic response. These studies also provide evidence that the increased phospholipid content of the lungs after exposure to NO2 is at least in part due to increased biosynthesis. The disaturated species of phosphatidylcholine increased preferentially over unsaturated species. Incorporation of [1-14C]palmitic acid into phosphatidylcholine reached a peak 36 h after exposure to NO2. The total amounts of phosphatidylcholine and phosphatidylglycerol, 2 components of lung surfactant lipid, were maximal at 48 h. By 4 days, the incorporation of [1-14C]palmitic acid into phosphatidylcholine returned to near normal values, and the phosphatidylcholine content of the lungs was still significantly increased at this time. Based on TLC and gas chromatography, no evidence was obtained for oxidation of esterified lipids or appearance of abnormal lipid structures in the lungs exposed to NO2.