Wren D R, Noble M
Department of Clinical Neurology, Institute of Neurology, Queen Square, London, United Kingdom.
Proc Natl Acad Sci U S A. 1989 Nov;86(22):9025-9. doi: 10.1073/pnas.86.22.9025.
The central nervous system of individuals with multiple sclerosis contains lesions specifically characterized by breakdown of myelin sheaths associated with a general failure of repair of demyelinating damage. The cause of myelin breakdown is unknown. Although immune mechanisms have been implicated in this breakdown, no convincing demonstrations of specific immune reaction against myelin have yet been provided in multiple sclerosis patients. Similarly, the cellular biological mechanisms which underlie the failure of myelin repair are unknown. We have found that (i) oligodendrocytes, the cells that produce myelin sheaths in the central nervous system, and (ii) oligodendrocyte/type-2 astrocyte (O/2A) progenitor cells derived from optic nerves of adult rats bind and activate complement in the absence of antibody in vitro, leading to destruction of these cells. Susceptibility to antibody-independent lysis by complement was a cell-type-specific trait of oligodendrocytes and adult O/2A progenitors and was not shared by perinatal O/2A progenitors, type-2 astrocytes, type-1 astrocytes, meningeal cells, or Schwann cells. We suggest that the susceptibility of oligodendrocytes and adult O/2A progenitor cells to complement-induced lysis, combined with other specific properties of adult O/2A progenitors, are consistent with--and may be a contributing factor--both in the generation of demyelinating lesions in multiple sclerosis and also in the failure of these lesions to be successfully repaired in adult multiple sclerosis patients.
患有多发性硬化症的个体的中枢神经系统存在病变，其具体特征是髓鞘破坏，同时伴有脱髓鞘损伤修复普遍失败。髓鞘破坏的原因尚不清楚。尽管免疫机制被认为与这种破坏有关，但在多发性硬化症患者中尚未有针对髓鞘的特异性免疫反应的确凿证据。同样，髓鞘修复失败背后的细胞生物学机制也不清楚。我们发现：（i）少突胶质细胞，即中枢神经系统中产生髓鞘的细胞；（ii）源自成年大鼠视神经的少突胶质细胞/2型星形胶质细胞（O/2A）祖细胞，在体外无抗体的情况下能结合并激活补体，导致这些细胞被破坏。对补体介导的非抗体依赖性裂解的易感性是少突胶质细胞和成年O/2A祖细胞的细胞类型特异性特征，围产期O/2A祖细胞、2型星形胶质细胞、1型星形胶质细胞、脑膜细胞或施万细胞则不具有这种特征。我们认为，少突胶质细胞和成年O/2A祖细胞对补体诱导裂解的易感性，结合成年O/2A祖细胞的其他特定特性，与多发性硬化症中脱髓鞘病变的产生以及成年多发性硬化症患者中这些病变未能成功修复均相符，并且可能是一个促成因素。
