Changes in innate and acquired immune responses in mice with targeted deletion of the dopamine transporter gene
Changes in innate and acquired immune responses in mice with targeted deletion of the dopamine transporter gene
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DOI：
10.1016/j.jneuroim.2005.01.004
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发表时间：
2005-04-01
影响因子：
3.3
通讯作者：
Heijnen, CJ
中科院分区：
文献类型：
--
作者：
Kavelaars, A;Cobelens, PM;Heijnen, CJ
多巴胺转运蛋白（DAT）负责将多巴胺重新摄取到突触前神经末梢，从而控制多巴胺能神经传递。 DAT 缺失会导致多巴胺能亢进表型，DAT(-/-) 小鼠的特征是垂体发育不全、母性行为受损和运动增加。从早期的研究中，我们有证据表明，中枢多巴胺能系统的活性可能在决定免疫反应性和疾病易感性方面发挥作用。为了进一步探讨多巴胺能系统与免疫系统之间的功能关系，我们研究了 DAT(-/-) 小鼠免疫系统的活性。我们发现，在体外，DAT(-/-) 小鼠的脾细胞表现出自然杀伤细胞活性降低和有丝分裂原诱导的细胞因子反应降低。相反，LPS诱导的巨噬细胞细胞因子的产生增强。在体内，对卵清蛋白免疫的细胞反应（OVA诱导的迟发型超敏反应）显着降低。有趣的是，与野生型动物相比，DAT(-/-) 小鼠中 OVA 诱导的体液反应（抗 OVA IgG）增加。 DAT(-/-) 和野生型动物之间儿茶酚胺和皮质酮的血浆水平没有显着差异。 总之，我们在本研究中表明，干扰多巴胺能系统对获得性和先天性免疫反应都有重大影响。 (C) 2005 Elsevier B.V. 保留所有权利。
The dopamine transporter (DAT) is responsible for the re-uptake of dopamine into presynaptic nerve terminals and thereby controls dopaminergic neurotransmission. Deletion of DAT results in a hyperdopaminergic phenotype and DAT(-/-) mice are characterized by pituitary hypoplasia, impaired maternal behavior, and increased locomotion. From earlier studies, we have evidence that the activity of the central dopaminergic system may play a role in determining immune reactivity and disease susceptibility. To further explore the functional relation between the dopaminergic system and the immune system, we investigated the activity of the immune system in DAT(-/-) mice. We show that in vitro, splenocytes from DAT(-/-) mice displayed reduced natural killer cell activity and reduced mitogen-induced cytokine responses. In contrast, LPS-induced cytokine production by macrophages was enhanced. In vivo, the cellular response to immunization with ovalbumine (OVA-induced delayed type hypersensitivity response) was significantly reduced. Interestingly, the OVA-induced humoral response (anti-OVA IgG) was increased in DAT(-/-) mice compared to wild-type animals. Plasma levels of catecholamines and corticosterone did not differ significantly between DAT(-/-) and wild-type animals.In conclusion, we show in the present study that interfering with the dopaminergic system has major consequences for both the acquired and the innate immune response. (C) 2005 Elsevier B.V. All rights reserved.