Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), 47003 Valladolid, Spain.
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Biomolecules. 2022 Dec 11;12(12):1851. doi: 10.3390/biom12121851.
Innate immune cells such as monocytes and macrophages contain high levels of arachidonic acid (AA), part of which can be mobilized during cellular activation for the formation of a vast array of bioactive oxygenated metabolites. Monocytes and macrophages present in inflammatory foci typically incorporate large amounts of AA, not only in membrane phospholipids, but also in neutral lipids such as triacylglycerol. Thus, it was of interest to investigate the metabolic fate of these two AA pools in macrophages. Utilizing a variety of radiolabeling techniques to distinguish the phospholipid and triacylglycerol pools, we show in this paper that during an acute stimulation of the macrophages with yeast-derived zymosan, the membrane phospholipid AA pool acts as the major, if not the only, source of releasable AA. On the contrary, the AA pool in triacylglycerol appears to be used at a later stage, when the zymosan-stimulated response has declined, as a source to replenish the phospholipid pools that were consumed during the activation process. Thus, phospholipids and triacylglycerol play different in roles AA metabolism and dynamics during macrophage activation.
先天免疫细胞,如单核细胞和巨噬细胞,含有高水平的花生四烯酸 (AA),其中一部分在细胞激活时可以被动员,形成大量的生物活性含氧代谢物。炎症灶中存在的单核细胞和巨噬细胞通常会大量摄取 AA,不仅存在于细胞膜磷脂中,还存在于三酰甘油等中性脂质中。因此,研究巨噬细胞中这两个 AA 池的代谢命运是很有意义的。利用各种放射性标记技术来区分磷脂和三酰甘油池,我们在本文中表明,在酵母来源的 zymosan 对巨噬细胞的急性刺激过程中,膜磷脂 AA 池作为可释放 AA 的主要(如果不是唯一)来源发挥作用。相反,在酵母聚糖刺激反应下降时,三酰甘油中的 AA 池似乎在后期被用作补充在激活过程中消耗的磷脂池的来源。因此,在巨噬细胞激活过程中,磷脂和三酰甘油在 AA 代谢和动态方面发挥不同的作用。