Abstract:
This work describes a novel route for phospholipid fatty acid remodeling involving the monounsaturated fatty acid palmitoleic acid. When administered to human monocytes, palmitoleic acid rapidly incorporates into membrane phospholipids, notably into phosphatidylcholine (PC). In resting cells, palmitoleic acid remains within the phospholipid pools where it was initially incorporated, showing no further movement. However, stimulation of the human monocytes with either receptor-directed (opsonized zymosan) or soluble (calcium ionophore A23187) agonists results in the rapid transfer of palmitoleic acid moieties from PC to phosphatidylinositol (PI). This is due to the activation of a coenzyme A-dependent remodeling route involving two different phospholipase A2 enzymes that act on different substrates to generate free palmitoleic acid and lysoPI acceptors. The stimulated enrichment of specific PI molecular species with palmitoleic acid unveils a hitherto-unrecognized pathway for lipid turnover in human monocytes which may play a role in regulating lipid signaling during innate immune activation.
摘要:
这项工作描述了涉及单不饱和脂肪酸棕榈油酸的磷脂脂肪酸重塑的新途径。当施用于人类单核细胞时,棕榈油酸迅速掺入膜磷脂,特别是磷脂酰胆碱(PC)。在静息细胞中,棕榈油酸保留在最初掺入的磷脂池中,没有进一步的运动。然而,用受体定向的(调理的酵母聚糖)或可溶性(钙离子载体A23187)激动剂刺激人单核细胞导致棕榈油酸部分从PC快速转移到磷脂酰肌醇(PI)。这是由于辅酶A依赖性重塑途径的激活,该途径涉及两种不同的磷脂酶A2酶,它们作用于不同的底物以产生游离的棕榈油酸和溶素PI受体。用棕榈油酸刺激特定PI分子物种的富集揭示了迄今为止未被识别的人单核细胞脂质周转途径,该途径可能在先天免疫激活期间调节脂质信号传导中起作用。