Nakano Y, Pross S, Klein T, Friedman H
University of South Florida College of Medicine, Tampa 33612.
Int J Immunopharmacol. 1993 Apr;15(3):423-8. doi: 10.1016/0192-0561(93)90054-3.
It has been previously shown that when mitogens such as concanavalin A (Con A) or phytohemagglutinin (PHA), are used to stimulate lymphoid cells which are treated with varying doses of delta-9-tetrahydrocannabinol (THC), the proliferation of splenocytes from mice of different ages is suppressed. In contrast, when these cells were stimulated with anti-CD3 antibody in combination with THC, lower doses of THC stimulated proliferation of the splenocytes. This stimulation occurred only if the spleens were obtained from adult (2 month) mice as opposed to cells from young (2 week) or aged (24 month) mice. In order to more completely understand this age related differential effect, mobilization of cytosolic free Ca2+ was studied in this system, using fluorescent Ca2+ probes and spectrofluorometry. It was found that adult splenocytes pretreated with anti-CD3 antibody responded to cross-linking by anti-IgG antibody with a further rise in intracellular free Ca2+. Such an increase in Ca2+ was not seen with cells derived from either young or old mice. A similar phenomenon occurred when 5 micrograms/ml THC was used in place of the anti-IgG antibody. Thus, adult spleen cells exposed to both delta-9-THC and anti-CD3 antibody displayed an increase in intracellular free calcium whereas spleen cells from very young mice failed to respond in this manner. Interestingly, when 11-hydroxy-THC, another metabolite of marijuana, was used instead of the delta-9-THC, no rise in intracellular Ca2+ influx was seen in any age group of mice tested. These results emphasize the differential effect of THC on splenocytes from individuals of different ages.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明，当使用诸如刀豆球蛋白A（Con A）或植物血凝素（PHA）等促细胞分裂剂刺激用不同剂量的δ-9-四氢大麻酚（THC）处理的淋巴细胞时，不同年龄小鼠的脾细胞增殖受到抑制。相比之下，当用抗CD3抗体与THC联合刺激这些细胞时，较低剂量的THC会刺激脾细胞增殖。这种刺激仅在从成年（2个月）小鼠获得的脾脏中出现，而不是来自幼年（2周）或老年（24个月）小鼠的细胞。为了更全面地了解这种与年龄相关的差异效应，在该系统中使用荧光钙探针和荧光分光光度法研究了胞质游离Ca2+的动员。结果发现，用抗CD3抗体预处理的成年脾细胞对抗IgG抗体的交联反应是细胞内游离Ca2+进一步升高。在来自幼年或老年小鼠的细胞中未观察到这种Ca2+的增加。当使用5微克/毫升的THC代替抗IgG抗体时，也出现了类似的现象。因此，暴露于δ-9-THC和抗CD3抗体的成年脾细胞显示细胞内游离钙增加，而非常年幼小鼠的脾细胞则没有这种反应。有趣的是，当使用大麻的另一种代谢产物11-羟基-THC代替δ-9-THC时，在任何测试年龄组的小鼠中均未观察到细胞内Ca2+流入增加。这些结果强调了THC对不同年龄个体脾细胞的差异效应。（摘要截断于250字）
