Richieri G V, Kleinfeld A M
Division of Membrane Biology, Medical Biology Institute, La Jolla, CA 92037.
J Immunol. 1990 Aug 15;145(4):1074-7.
Short term exposure of murine CTL clones to long chain cis unsaturated free fatty acid (FFA) inhibits alloantigen specific lysis of cognate target cells, whereas long-chain saturated FFA have no effect. Inhibition of lysis occurs when cis FFA is added before or within 10 min after CTL-target cell conjugate formation and thus appears to interfere with lethal hit delivery. Our previous studies have shown that similar treatment with cis FFA inhibits, in CTL, the Ag stimulated increase in intracellular calcium and degranulation, suggesting that inhibition of lysis probably results from perturbation of the CTL signaling pathway. However, inhibition of lysis is probably not due to the inhibition of the rise in intracellular calcium or degranulation, because lysis can occur under conditions in which FFA inhibit degranulation and because cis FFA inhibit calcium-independent killing. Inhibition of lysis is detectable at unbound FFA concentrations less than 1 microM and is generally complete at concentrations less than 5 microM. Although these levels of FFA are somewhat higher than reported for normal physiologic conditions, plasma FFA levels can be elevated into this range in states of stress and disease, suggesting that FFA modulation of the immune response has important physiologic consequences.
将小鼠细胞毒性T淋巴细胞（CTL）克隆短期暴露于长链顺式不饱和游离脂肪酸（FFA）会抑制同源靶细胞的同种异体抗原特异性裂解，而长链饱和FFA则无此作用。当在CTL与靶细胞结合形成共轭体之前或之后10分钟内添加顺式FFA时，裂解会受到抑制，因此似乎干扰了致死性打击的传递。我们之前的研究表明，用顺式FFA进行类似处理会抑制CTL中抗原刺激引起的细胞内钙增加和脱颗粒，这表明裂解受到抑制可能是由于CTL信号通路受到干扰。然而，裂解受到抑制可能并非由于细胞内钙升高或脱颗粒受到抑制，因为在FFA抑制脱颗粒的条件下仍可发生裂解，而且顺式FFA会抑制不依赖钙的杀伤作用。在游离FFA浓度低于1微摩尔时即可检测到裂解受到抑制，而在浓度低于5微摩尔时通常完全受到抑制。尽管这些FFA水平略高于正常生理条件下的报道水平，但在应激和疾病状态下，血浆FFA水平可升高至这一范围，这表明FFA对免疫反应的调节具有重要的生理意义。
