Madden K S, Ackerman K D, Livnat S, Felten S Y, Felten D L
Department of Neurobiology, University of Rochester School of Medicine and Dentistry, New York 14642.
Brain Behav Immun. 1993 Dec;7(4):344-51. doi: 10.1006/brbi.1993.1034.
The development of natural killer (NK) cell activity was assessed in Fischer 344 (F344) rats sympathectomized as neonates with the neurotoxin, 6-hydroxydopamine (6-OHDA). No NK cell activity was detected in sympathectomized or vehicle-injected control animals at 7 days of age. At 10 and 14 days of age, NK cell activity was reduced in spleens from sympathectomized male and female rats. At 21 days of age, a reduction in NK cell activity was detected only in sympathectomized male rats. Sympathectomy did not alter NK cell activity at 28 and 42 days of age in either gender. At 56 days of age, NK cell activity was increased in neonatally sympathectomized females; rats of both genders acutely sympathectomized at 56 days of age also showed enhanced NK cell activity. No differences were observed at 90 days of age in neonatally or acutely sympathectomized males of females. Prior treatment with desipramine, which blocks uptake of 6-OHDA into nerve terminals and prevents the destruction of sympathetic nerve terminals, prevented these 6-OHDA-induced effects, suggesting that sympathectomy, and not direct toxic effects of 6-OHDA treatment of NK cells, accounted for the alterations in NK cell activity. Together, these results indicate that the sympathetic nervous system is an integral component of the developing lymphoid and hematopoietic microenvironment.
利用神经毒素6-羟基多巴胺(6-OHDA)对新生Fischer 344(F344)大鼠进行交感神经切除术,以此评估自然杀伤(NK)细胞活性的发育情况。在7日龄时,交感神经切除的动物或注射赋形剂的对照动物均未检测到NK细胞活性。在10日龄和14日龄时,交感神经切除的雄性和雌性大鼠脾脏中的NK细胞活性降低。在21日龄时,仅在交感神经切除的雄性大鼠中检测到NK细胞活性降低。交感神经切除术在28日龄和42日龄时未改变任何性别的NK细胞活性。在56日龄时,新生期交感神经切除的雌性大鼠的NK细胞活性增加;56日龄时急性交感神经切除的两性大鼠也表现出NK细胞活性增强。在90日龄时,新生期或急性交感神经切除的雄性或雌性大鼠均未观察到差异。预先用去甲丙咪嗪治疗,该药物可阻止6-OHDA摄取到神经末梢并防止交感神经末梢的破坏,可预防这些6-OHDA诱导的效应,这表明是交感神经切除术而非6-OHDA对NK细胞的直接毒性作用导致了NK细胞活性的改变。总之,这些结果表明交感神经系统是发育中的淋巴和造血微环境的一个组成部分。