En Junichiro, Ishii Norihisa, Goto Masamichi
National Sanatorium Hoshizuka-Keiaien, Kagoshima, Japan.
Nihon Hansenbyo Gakkai Zasshi. 2011 Feb;80(1):5-10. doi: 10.5025/hansen.80.5.
Buruli ulcer is a skin disease caused by Mycobacterium ulcerans (M. ulcerans). In this review, we introduce our recent studies and other important works. Lesions of Buruli ulcer are usually painless, despite the extensive tissue necrosis. We have reported that mice inoculated with M ulcerans show nerve degeneration and absence of pain, but the mechanism evoking the nerve damage have not been clarified. In order to define whether mycolactone, a toxic lipid produced by M. ulcerans, can induce nerve damages, we have injected mycolactone A/B to BALB/c mouse footpads. Mycolactone induced footpad swelling, and sensory test showed hyperesthesia on day 7 and 14, recovery on day 21, and hypoesthesia on days 28 and 42. Histologically, nerve bundles showed hemorrhage, neutrophilic infiltration, and loss of Schwann cell nuclei on days 7 and 14. Semithin section studies revealed vacuolar change of Schwann cells started on day 14, which subsided by day 42, but myelinated fiber density remained low. This study suggests that mycolactone directly damages nerves and is responsible for the absence of pain characteristic of Buruli ulcer. In the human lesions, presence of neuritis is reported (Rondini S, 2006), and murine studies showed "autoamputation" (Addo P, 2005). In order to prevent the serious deformities evoked by Buruli ulcer, further studies are necessary.
布氏杆菌溃疡是一种由溃疡分枝杆菌引起的皮肤病。在本综述中，我们介绍了我们最近的研究以及其他重要工作。尽管布氏杆菌溃疡会导致广泛的组织坏死，但其病变通常无痛。我们曾报道，接种溃疡分枝杆菌的小鼠会出现神经退化且无痛觉，但引发神经损伤的机制尚未阐明。为了确定溃疡分枝杆菌产生的一种有毒脂质——毒素内酯是否能诱导神经损伤，我们将毒素内酯A/B注射到BALB/c小鼠的脚垫中。毒素内酯导致脚垫肿胀，感觉测试显示在第7天和第14天出现感觉过敏，第21天恢复，第28天和第42天出现感觉减退。组织学上，在第7天和第14天，神经束出现出血、嗜中性粒细胞浸润以及施万细胞核的丢失。半薄切片研究显示，施万细胞的空泡化变化在第14天开始，到第42天消退，但有髓纤维密度仍然较低。这项研究表明，毒素内酯直接损伤神经，并且是布氏杆菌溃疡无痛特征的原因。在人类病变中，有神经炎存在的报道（Rondini S，2006年），而小鼠研究显示有“自截现象”（Addo P，2005年）。为了预防布氏杆菌溃疡引起的严重畸形，还需要进一步研究。
