Wege H, Schluesener H, Meyermann R, Barac-Latas V, Suchanek G, Lassmann H
Federal Research Centre for Virus Diseases of Animals, Friedrich-Loeffler-Institutes, Isle of Riems, Austria.
Adv Exp Med Biol. 1998;440:437-44.
Coronavirus infections of rodents can cause diseases of the central nervous system characterised by inflammatory demyelination. The lesions mimick in many aspects the pathology of multiple sclerosis in humans and of other neurological diseases. As an animal model for demyelination, we studied the MHV-JHM induced encephalomyelitis of Lewis rats. The pathomorphological analysis revealed patterns of lesions which developed in stages. Infected oligodendrocytes were first destroyed by necrosis. Later stages were characterized by demyelinated plaques. In the center of plaques, no virus antigen was found and oligodendrocytes were mainly destroyed by apoptosis. At the edge of plaques, virus antigen was expressed in parallel to infiltrations consisting of lymphocytes and macrophages. The prevailing mechanisms leading to demyelination may change individually and during defined stages of the disease. The transcriptional expression of chemoattractants and other mediators of inflammation was studied by semiquantitative RT-PCR. Virus induced inflammatory demyelination was accompanied by high expression of a relatively novel cytokine, the endothelial monocyte activating polypeptide II (EMAP II). By immunocytochemistry, EMAP II was detected in parenchymal microglia located both within the lesions and in unaffected areas. Furthermore, the level of transcriptional expression of the regulatory calcium binding S100 proteins MRP8, MRP14 and CP10 was associated with inflammatory demyelination and expression of IFN gamma, IL-2, TNF alpha, and iNOS.
啮齿动物的冠状病毒感染可引发以炎症性脱髓鞘为特征的中枢神经系统疾病。这些病变在许多方面类似于人类多发性硬化症及其他神经疾病的病理学表现。作为脱髓鞘的动物模型，我们研究了由MHV-JHM诱导的Lewis大鼠脑脊髓炎。病理形态学分析揭示了病变呈阶段性发展的模式。受感染的少突胶质细胞首先因坏死而被破坏。后期阶段的特征是脱髓鞘斑块。在斑块中心，未发现病毒抗原，少突胶质细胞主要因凋亡而被破坏。在斑块边缘，病毒抗原与由淋巴细胞和巨噬细胞组成的浸润同时表达。导致脱髓鞘的主要机制可能在疾病的特定阶段单独发生变化。通过半定量RT-PCR研究趋化因子和其他炎症介质的转录表达。病毒诱导的炎症性脱髓鞘伴随着一种相对新的细胞因子——内皮单核细胞激活多肽II（EMAP II）的高表达。通过免疫细胞化学方法，在病变内和未受影响区域的实质小胶质细胞中均检测到了EMAP II。此外，调节性钙结合S100蛋白MRP8、MRP14和CP10的转录表达水平与炎症性脱髓鞘以及IFNγ、IL-2、TNFα和iNOS的表达相关。
