Benyon R C, Church M K, Holgate S T
Immunopharmacology Group, University of Southampton, United Kingdom.
J Immunol. 1988 Aug 1;141(3):954-60.
Enhanced phospholipid methylation has been suggested to be an obligatory process in IgE-dependent stimulus-secretion coupling in human lung mast cells. Our studies with mast cell-enriched lung preparations do not support this hypothesis, demonstrating no increased 3H-methyl radiolabeling of chloroform/methanol-extracted lipids or chromatographically separated phospholipids accompanying anti-IgE-dependent histamine secretion. Inhibitors of transmethylation, 3-deazaadenosine, and homocysteine thiolactone inhibited histamine secretion by both anti-IgE and calcium ionophore A23187, reflecting a requirement of secretion for overall integrity of cellular transmethylation. These agents induced small increases in cAMP concentration which are considered to make at most a minor contribution to this inhibition. The inability of methylation inhibitors to diminish anti-IgE-dependent increases in lung mast cell cAMP levels would suggest that not only does phospholipid methylation have no role in histamine secretion but also it does not participate in the activation of adenylate cyclase by this stimulus.
增强的磷脂甲基化被认为是人类肺肥大细胞中IgE依赖性刺激-分泌偶联的一个必要过程。我们对富含肥大细胞的肺组织制剂的研究不支持这一假设，未显示伴随抗IgE依赖性组胺分泌，氯仿/甲醇提取的脂质或色谱分离的磷脂的3H-甲基放射性标记增加。转甲基化抑制剂3-脱氮腺苷和高半胱氨酸硫内酯抑制抗IgE和钙离子载体A23187诱导的组胺分泌，反映出分泌需要细胞转甲基化的整体完整性。这些药物使cAMP浓度小幅增加，而这被认为对此种抑制作用至多只起很小的作用。甲基化抑制剂无法减少肺肥大细胞中抗IgE依赖性cAMP水平的增加，这表明不仅磷脂甲基化在组胺分泌中不起作用，而且它也不参与这种刺激对腺苷酸环化酶的激活。
