Chronic self-administration of nicotine in rats impairs T cell responsiveness.
Chronic self-administration of nicotine in rats impairs T cell responsiveness.
复制标题
DOI：
10.1124/jpet.302.3.935
复制
发表时间：
2002-09
期刊：
影响因子：
--
通讯作者：
Roma Kalra;S. Singh;D. Kracko;S. Matta;B. Sharp;M. Sopori
中科院分区：
文献类型：
--
作者：
Roma Kalra;S. Singh;D. Kracko;S. Matta;B. Sharp;M. Sopori
啮齿动物通过皮下或脑室内植入的微渗泵长期接触尼古丁会影响 T 细胞功能。然而，这种连续尼古丁施用的方法并不能复制人类吸烟者自我激励的尼古丁施用。为了确定尼古丁在与人类吸烟者相关的条件下是否会损害免疫系统，我们使用几乎无限获取尼古丁的模型，研究了雄性Lewis大鼠自我施用（SA）尼古丁（每次注射0.03毫克/公斤体重）40至50次/天，持续5周的T细胞反应性。与假手术对照动物相比，伴刀豆球蛋白A诱导的SA大鼠脾细胞增殖显着降低。此外，SA中T细胞抗原受体(TCR)与抗αβTCR抗体连接后，脾细胞调动细胞内Ca(2+)的能力显着低于对照大鼠。此外，SA 动物的脾细胞中肌醇 1,4,5-三磷酸 (IP(3)) 敏感的细胞内 Ca(2+) 储存明显减少。这些结果表明，长期尼古丁自我给药会抑制T细胞反应性，这种抑制可能是由于IP(3)敏感的细胞内Ca(2+)储备耗尽而导致TCR介导的信号传导受损所致。
Chronic exposure of rodents to nicotine via subcutaneously or intracerebroventricularly implanted miniosmotic pumps affects T cell function. However, this method of continuous nicotine administration does not replicate the self-motivated administration of nicotine in human smokers. To determine whether nicotine impairs the immune system under conditions pertinent to human smokers, we investigated the T cell responsiveness of male Lewis rats self-administering (SA) nicotine (0.03 mg/kg of body weight per injection) 40 to 50 times/day for 5 weeks, using a model of virtually unlimited access to nicotine. Compared with sham control animals, the concanavalin A-induced proliferation of spleen cells from SA rats was significantly decreased. Moreover, the ability of spleen cells to mobilize intracellular Ca(2+) after ligation of the T cell antigen receptor (TCR) with an anti-alphabeta TCR antibody was significantly less in SA than in control rats. In addition, inositol 1,4,5-trisphosphate (IP(3))-sensitive intracellular Ca(2+) stores were markedly depleted in spleen cells from SA animals. These results suggest that chronic nicotine self-administration suppresses T cell responsiveness, and this suppression may result from an impaired TCR-mediated signaling that stems from the depletion of IP(3)-sensitive intracellular Ca(2+) stores.