Naba I, Yoshikawa H, Sakoda S, Itabe H, Suzuki H, Kodama T, Yanagihara T
Department of Neurology D4, Osaka University Graduate School of Medicine.
Exp Neurol. 2000 Nov;166(1):83-9. doi: 10.1006/exnr.2000.7495.
Onion-bulb (OB) formation is often encountered in acquired neuropathies such as chronic inflammatory demyelinating polyradiculoneuropathy and diabetic neuropathy and is believed to require repeated injuries to peripheral nerves. Although this suggests that remaining damaged cell membranes, including myelin debris, might trigger OB formation, the molecular mechanism remains unclear. In this study, we were successful in producing many small OBs after a single compression injury to peripheral nerves of the knockout mice deficient of macrophage scavenger receptor class A (MSR-A). Although morphometry showed no difference in the average densities of the remaining myelinating fibers between wild-type and MSR-A knockout mice after the compression injury, there were more macrophages and myelin debris positive for oxidized-phosphatidylcholine in the nerves from the MSR-A knockout mice. We believe that OB formation was induced after a single compression injury as the result of delayed phagocytosis of myelin debris possessing oxidized lipids by MSR-A deficient macrophages. The present work shed light on the molecular mechanism of OB formation seen in chronic neuropathies and provided a model for further investigation.
洋葱球（OB）形成常见于慢性炎症性脱髓鞘性多发性神经根神经病和糖尿病性神经病等获得性神经病变中，并且被认为需要对周围神经反复造成损伤。尽管这表明包括髓磷脂碎片在内的残留受损细胞膜可能触发OB形成，但其分子机制仍不清楚。在本研究中，我们对缺乏A类巨噬细胞清道夫受体（MSR-A）的基因敲除小鼠的周围神经进行单次压迫损伤后，成功产生了许多小的OB。尽管形态测量显示，压迫损伤后野生型小鼠和MSR-A基因敲除小鼠之间剩余有髓纤维的平均密度没有差异，但MSR-A基因敲除小鼠神经中的巨噬细胞和氧化磷脂酰胆碱阳性的髓磷脂碎片更多。我们认为，由于MSR-A缺陷巨噬细胞对含有氧化脂质的髓磷脂碎片的吞噬作用延迟，单次压迫损伤后诱导了OB形成。本研究揭示了慢性神经病变中OB形成的分子机制，并为进一步研究提供了一个模型。
