Park E-S, Uchida K, Nakayama H
Department of Veterinary Pathology, Faculty of Agriculture, University of Tokyo, Tokyo 113-8657, Japan. Email:
Vet Pathol. 2013 Nov;50(6):1127-34. doi: 10.1177/0300985813488957. Epub 2013 May 7.
Necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME) are idiopathic inflammatory diseases in the central nervous system (CNS) of dogs. In our previous study, the proportion of inflammatory cells, except for CD3-positive T cells, were not different in parenchymal and perivascular lesions in the brain. However, breed specificities, clinical courses, and specific lesions were distinct among these diseases. Thus, similarities and differences in the pathologies of these diseases have been implied. In this study, the messenger RNA (mRNA) and/or protein expression levels of cytokines and chemokine receptors were investigated in NME (n = 2), NLE (n = 4), and GME (n = 2) cases, and their relationship in the formation of specific lesions was discussed. The mRNA and protein expression levels of interferon (IFN)-γ and interleukin (IL)-17 were marked in NME and GME, respectively. The mRNA expression levels of CXCR3 and CCR2 were also marked in NME and GME, respectively. The results of double-labeling immunofluorescence, used to identify cells producing IL-17 in these lesions, showed that most CD163-positive macrophages/microglia but fewer CD3-positive T cells were IL-17 positive in GME. These results indicate that IFN-γ plays a key role in NME lesions and that the macrophages/microglia that infiltrate brain lesions producing IL-17 are more important in GME than T cells.
坏死性脑膜脑炎(NME)、坏死性白质脑炎(NLE)和肉芽肿性脑膜脑脊髓炎(GME)是犬中枢神经系统(CNS)的特发性炎症性疾病。在我们之前的研究中,除CD3阳性T细胞外,脑实质和血管周围病变中的炎症细胞比例并无差异。然而,这些疾病在品种特异性、临床病程和特定病变方面存在明显差异。因此,这些疾病在病理学上的异同已被暗示。在本研究中,我们调查了NME(n = 2)、NLE(n = 4)和GME(n = 2)病例中细胞因子和趋化因子受体的信使核糖核酸(mRNA)和/或蛋白质表达水平,并讨论了它们在特定病变形成中的关系。干扰素(IFN)-γ和白细胞介素(IL)-17的mRNA和蛋白质表达水平分别在NME和GME中显著升高。CXCR3和CCR2的mRNA表达水平也分别在NME和GME中显著升高。用于识别这些病变中产生IL-17的细胞的双重免疫荧光标记结果显示,在GME中,大多数CD163阳性巨噬细胞/小胶质细胞呈IL-17阳性,但CD3阳性T细胞呈IL-17阳性的较少。这些结果表明,IFN-γ在NME病变中起关键作用,并且浸润脑病变产生IL-17的巨噬细胞/小胶质细胞在GME中比T细胞更重要。