Kirkland J B, Bray T M
Proc Soc Exp Biol Med. 1984 Jan;175(1):30-4. doi: 10.3181/00379727-175-41761.
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 dependent 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 microM to 10 microM 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.
3-甲基吲哚（3MI）是色氨酸的瘤胃发酵产物，是急性牛肺水肿（ABPE）发病的病原体。该疾病依赖于混合功能氧化酶（MFO）对3MI的激活。电子显微镜照片显示，II型细胞的板层小体结构被破坏，含有中性脂质（NL）而非表面活性物质磷脂（PL）。使用山羊肺切片研究3MI诱导的PL代谢变化。从每个肺中切下18片，分为对照组、3MI（0.57 mM）组和吲哚（0.57 mM）组。用这些化合物预处理3小时后，将切片与[14C]乙酸一起孵育。提取并分离脂质。3MI抑制[14C]乙酸掺入所有研究的PL中，但对其掺入NL的影响很小。吲哚对膜的作用与3MI相同，但不被MFO系统激活，也不诱导肺损伤。吲哚预处理对任何脂质组分中乙酸掺入的影响很小。这些结果表明，肺切片中3MI的代谢是体外PL合成受抑制的原因。将培养基中未标记胆碱的水平从10 microM提高到10 microM对[14C]乙酸掺入磷脂酰胆碱（PC）的抑制没有影响。这表明胆碱摄取不是3MI处理的肺切片中PC合成的限制因素。
