Transcellular biosynthesis of cysteinyl leukotrienes in rat neuronal and glial cells
Transcellular biosynthesis of cysteinyl leukotrienes in rat neuronal and glial cells
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DOI：
10.1111/j.1471-4159.2007.04830.x
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发表时间：
2007-11-01
影响因子：
4.7
通讯作者：
Heidenreich, Kim A.
中科院分区：
文献类型：
--
作者：
Farias, Santiago E.;Zarini, Simona;Heidenreich, Kim A.
白三烯是炎症介质，属于通过5-脂氧合酶作用从花生四烯酸衍生的脂质家族。已在中枢神经系统中检测到与不同病理事件相关的白三烯，但对其在脑中的生物合成或功能知之甚少。当大鼠神经元和神经胶质细胞在原代培养物中的钙离子载体刺激，没有显着的生物合成的白三烯检测使用液相色谱/质谱（LC/MS）技术。然而，当将外源性LTA（4）加入到这些培养的细胞中时，神经元和神经胶质都能够合成LTC 4。已知活化的中性粒细胞向其他细胞提供LTA（4），用于半胱氨酰-白三烯的跨细胞生物合成。由于中性粒细胞可以在中风或创伤性脑损伤后浸润脑组织，我们研究了中性粒细胞是否在中枢神经系统中发挥类似的作用。当外周血中性粒细胞与大鼠神经元，神经胶质细胞共培养，然后用钙离子载体刺激时，观察到LTC 4，LTD 4和LTE 4的稳健产生，揭示神经元和神经胶质细胞可以参与白三烯生物合成的跨细胞机制。通过这种机制形成的LTC 4可能与脑损伤引起的炎症反应的发生和进展有关。
Leukotrienes are mediators of inflammation that belong to a family of lipids derived from arachidonic acid by the action of 5-lipoxygenase. Leukotrienes have been detected in the central nervous system in association with different pathological events, but little is known about their biosynthesis or function in the brain. When rat neurons and glial cells in primary culture were stimulated with the calcium ionophore, no significant biosynthesis of leukotrienes was detected using liquid chromatography/mass spectrometry (LC/MS) techniques. However, when exogenous LTA(4) was added to these cultured cells, both neurons and glia were able to synthesize LTC4. Activated neutrophils are known to supply LTA(4) to other cells for transcellular biosynthesis of cysteinyl-leukotrienes. Since neutrophils can infiltrate brain tissue after stroke or traumatic brain injury, we examined whether neutrophils play a similar role in the central nervous system. When peripheral blood neutrophils were co-cultured with rat neurons, glia cells, and then stimulated with calcium ionophore, a robust production of LTC4, LTD4, and LTE4 was observed, revealing that neurons and glia can participate in the transcellular mechanism of leukotriene biosynthesis. The formation of LTC4 through this mechanism may be relevant in the genesis and progression of the inflammatory response as a result of brain injury.