Aging and sympathetic modulation of immune function in Fischer 344 rats: Effects of chemical sympathectomy on primary antibody response
Aging and sympathetic modulation of immune function in Fischer 344 rats: Effects of chemical sympathectomy on primary antibody response
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DOI：
10.1016/j.jneuroim.2005.03.022
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发表时间：
2005-08-01
影响因子：
3.3
通讯作者：
Madden, KS
中科院分区：
文献类型：
--
作者：
Bellinger, DL;Stevens, SY;Madden, KS
在老年Fischer 344（F334）大鼠中，与年轻大鼠相比，脾脏的交感神经支配明显减少。为了确定这种减少的去甲肾上腺素能（NA）神经支配是否保持与免疫系统的功能连接，用NA选择性神经毒素6-羟基多巴胺（6-OHDA）治疗3个月和17个月大的雄性F344大鼠，以消融外周NA神经纤维。在交感神经切除大鼠免疫与钥孔血蓝蛋白（KLH），T依赖性蛋白抗原，抗KLH IgM，IgG，IgG 1，IgG 2b抗体滴度增加，在年轻和老年大鼠免疫后14天相比，溶剂对照。此外，IgM和IgG抗KLH抗体分泌脾细胞的数量在免疫后7天和14天升高。这些影响被预防预处理与地昔帕明，一种儿茶酚胺摄取阻滞剂，阻断6-OHDA摄取和随后的交感神经切除术。化学交感神经切除术也增加了KLH诱导的增殖体外脾细胞从老，但不是年轻的动物。异丙肾上腺素（ISO），β-肾上腺素能受体激动剂，引起了从NA完整的年轻和老年大鼠脾细胞cAMP的增加，但从老年大鼠脾细胞的增加减弱。这些结果表明，虽然NA神经支配的F344大鼠脾脏随着年龄的增长而减少，交感神经信号的免疫系统保持完整。因此，SNS可以抑制年轻和年老的F344大鼠中响应于蛋白质抗原产生的抗体。(C)2005 Elsevier B. V.保留所有权利。
In aged Fischer 344 (F334) rats, sympathetic innervation of the spleen is markedly diminished compared with young rats. To determine if this diminished noradrenergic (NA) innervation maintains a functional connection with the immune system, 3- and 17-month-old male F344 rats were treated with the NA-selective neurotoxin, 6-hydroxydopamine (6-OHDA), to ablate peripheral NA nerve fibers. In sympathectomized rats immunized with keyhole limpet hemocyanin (KLH), a T-dependent protein antigen, anti-KLH IgM, IgG, IgG1, IgG2b antibody titers were increased in young and old rats 14 days after immunization compared to vehicle controls. Furthermore, the number of IgM and IgG anti-KLH antibody-secreting spleen cells was elevated 7 and 14 days post-immunization. These effects were prevented by pretreatment with desipramine, a catecholamine uptake blocker that blocks 6-OHDA uptake and subsequent sympathectomy. Chemical sympathectomy also increased KLH-induced proliferation in vitro by spleen cells from old, but not young animals. Isoproterenol (ISO), a beta-adrenergic receptor agonist, elicited a rise in cAMP in spleen cells from NA-intact young and old rats, but the increase was attenuated in spleen cells from old rats. These results demonstrate that, although NA innervation in the F344 rat spleen is diminished with age, sympathetic signaling of the immune system remains intact. Thus, the SNS can inhibit antibody produced in response to a protein antigen in both young and old F344 rats. (C) 2005 Elsevier B.V. All rights reserved.