The Effect of 3-Methylindole on Phospholipid Synthesis in Goat Lung Tissue Slices 1

Abstract

3-Methylindole (3MI), a ruminal fermentation product of tryptophan, is the causative agent in the development of acute bovine pulmonary edema (ABPE). The disease is dependant on the activation of 3MI by mixed function oxidases (MFO). Electron micrographs have revealed that the lamellar bodies of the type II cells are disrupted in structure and contain neutral lipids (NL) instead of surfactant phospholipids (PL). Goat lung slices were used to investigate the changes in PL metabolism induced by 3MI. Eighteen slices were cut from each lung and divided into control, 3MI (0.57 mM), and indole (0.57 mM) groups. After a 3-hr pretreatment with these compounds, the slices were incubated with [¹⁴C]acetate. The lipids were extracted and separated. 3MI inhibited the incorporation of [¹⁴C]acetate into all of the PL studied, but had little effect on its incorporation into NL. Indole displays the same effects on membranes as 3MI, but is not activated by the MFO system and does not induce lung injury. Indole pretreatment had little effect on acetate incorporation in any of the lipid fractions. These results indicate that metabolism of 3MI in lung slices is responsible for the depression of PL synthesis in vitro. Increasing the level of unlabeled choline in the medium from 10 μM to 10 mM had no effect on the depression of [¹⁴C]acetate incorporation into phosphatidylcholine (PC). This suggests that choline uptake is not limiting the synthesis of PC in the 3MI-treated lung slices.