Lanfranco Maria Fe, Mocchetti Italo, Burns Mark P, Villapol Sonia
Laboratory of Preclinical Neurobiology, Georgetown University Medical Center, Washington, DC, United States.
Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States.
Front Neuroanat. 2018 Jan 12;11:137. doi: 10.3389/fnana.2017.00137. eCollection 2017.
Chemokine (C-C motif) ligand 5 (CCL5) belongs to a group of chemokines that play a role in the peripheral immune system, mostly as chemoattractant molecules, and mediate tactile allodynia. In the central nervous system (CNS), CCL5 and its receptors have multiple functions, including promoting neuroinflammation, insulin signaling, neuromodulator of synaptic activity and neuroprotection against a variety of neurotoxins. Evidence has also suggested that this chemokine may regulate opioid response. The multifunctional profile of CCL5 might correlate with its ability to bind different chemokine receptors, as well as with its unique cellular expression. In this work, we have used fluorescence hybridization combined with immunohistochemistry to examine the expression profile of CCL5 mRNA in the adult rat brain and provide evidence of its cellular localization. We have observed that the highest expression of CCL5 mRNA occurs in all major fiber tracts, including the corpus callosum, anterior commissure, and cerebral peduncle. In these tracts, CCL5 mRNA was localized in oligodendrocytes, astrocytes and microglia. Astrocytic and microglial expression was also evident in several brain areas including the cerebral cortex, caudate/putamen, hippocampus, and thalamus. Furthermore, using a specific neuronal marker, we observed CCL5 mRNA expression in discrete layers of the cortex and hippocampus. Interestingly, in the midbrain, CCL5 mRNA co-localized with tyrosine hydroxylase (TH) positive cells of the ventral tegmental area, suggesting that CCL5 might be expressed by a subset of dopaminergic neurons of the mesolimbic system. The expression of CCL5 mRNA and protein, together with its receptors, in selected brain cell populations proposes that this chemokine could be involved in neuronal/glial communication.
趋化因子（C-C基序）配体5（CCL5）属于一组趋化因子，它们在外周免疫系统中发挥作用，主要作为化学引诱分子，并介导触觉异常性疼痛。在中枢神经系统（CNS）中，CCL5及其受体具有多种功能，包括促进神经炎症、胰岛素信号传导、突触活动的神经调节以及对多种神经毒素的神经保护作用。证据还表明，这种趋化因子可能调节阿片类反应。CCL5的多功能特性可能与其结合不同趋化因子受体的能力以及其独特的细胞表达有关。在这项研究中，我们使用荧光杂交结合免疫组织化学来检查成年大鼠脑中CCL5 mRNA的表达谱，并提供其细胞定位的证据。我们观察到CCL5 mRNA在所有主要纤维束中表达最高，包括胼胝体、前连合和大脑脚。在这些纤维束中，CCL5 mRNA定位于少突胶质细胞、星形胶质细胞和小胶质细胞。星形胶质细胞和小胶质细胞的表达在包括大脑皮层、尾状核/壳核、海马体和丘脑在内的几个脑区也很明显。此外，使用特定的神经元标记物，我们在皮层和海马体的离散层中观察到CCL5 mRNA的表达。有趣的是，在中脑，CCL5 mRNA与腹侧被盖区的酪氨酸羟化酶（TH）阳性细胞共定位，表明CCL5可能由中脑边缘系统的一部分多巴胺能神经元表达。CCL5 mRNA和蛋白质及其受体在选定的脑细胞群体中的表达表明，这种趋化因子可能参与神经元/胶质细胞通讯。
