Walker N I, Bennett R E, Axelsen R A
Department of Pathology, University of Queensland, Herston, Australia.
Am J Pathol. 1988 Jun;131(3):465-76.
A condition closely resembling human melanosis coli was induced in the guinea pig large intestine by daily oral administration of the anthraquinone danthron. Each treatment caused a transient, dose-related wave of apoptosis of the colonic surface epithelial cells. Most of the resulting apoptotic bodies were phagocytosed by intraepithelial macrophages and carried by them through fenestrae in the epithelial basement membrane to the lamina propria. Here, the apoptotic bodies were transformed into typical lipofuscin pigment in macrophage heterolysosomes. Continued danthron administration caused progressive accumulation of pigmented macrophages in the bowel wall, whereas ongoing migration of pigmented macrophages to regional lymph nodes resulted, after danthron was ceased, in sequential loss of the pigmented cells from the superficial and deep lamina propria. Examination of colonic biopsies from patients with melanosis coli shows increased numbers of apoptotic bodies in the surface epithelium and lamina propria, suggesting implication of the same cellular processes in the formation of the pigment in man.
通过每日口服蒽醌类药物丹蒽醌，在豚鼠大肠中诱导出一种与人类结肠黑变病极为相似的病症。每次治疗都会引发结肠表面上皮细胞出现短暂的、与剂量相关的凋亡波。大多数产生的凋亡小体被上皮内巨噬细胞吞噬，并由它们通过上皮基底膜的窗孔携带至固有层。在此处，凋亡小体在巨噬细胞异噬溶酶体中转化为典型的脂褐素色素。持续给予丹蒽醌会导致肠壁中色素沉着巨噬细胞逐渐积累，而在停止使用丹蒽醌后，色素沉着巨噬细胞持续向局部淋巴结迁移，导致固有层浅层和深层的色素沉着细胞相继丢失。对结肠黑变病患者的结肠活检进行检查发现，表面上皮和固有层中凋亡小体数量增加，这表明相同的细胞过程参与了人类色素的形成。
