Ultrastructure of rat lung following inhalation of ricin aerosol
Ultrastructure of rat lung following inhalation of ricin aerosol
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DOI：
10.1046/j.1365-2613.1997.300363.x
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发表时间：
1997-08-01
影响因子：
3
通讯作者：
White, DE
中科院分区：
文献类型：
--
作者：
Brown, RFR;White, DE
蓖麻毒素是一组结构相关的植物凝集素之一，被提取。各组大鼠吸入蓖麻毒素气雾剂，总LCt(1) = 11.21 mg.min。m(-3)（近似LCt（30）暴露），并在暴露后48小时内使用透射电子显微镜进行检查。暴露后6 - 12小时，肺泡巨噬细胞出现超微结构改变的最初迹象，主要表现为细胞核的凋亡改变。这些包括核周围的异染色质凝聚和核膜的粗缩。暴露后12和15小时，肺泡壁和血/气屏障细胞发生一系列变化，最终导致肺泡内水肿。首先在毛细血管内皮中观察到损伤，从暴露后12小时开始，I型上皮细胞发生明显变化。这些变化在本质上似乎是坏死而不是凋亡，这表明除了蓖麻毒素的直接作用外，可能还涉及其他机制。与这些变化相关的是间质中混合炎症细胞浸润，孤立的II型肺细胞坏死和微血管微血栓形成的证据。暴露48小时后，肺泡内水肿明显减轻，II型肺细胞增生明显。发现肺泡巨噬细胞凋亡在蓖麻毒素中毒机制中起重要作用，为开发新的蓖麻毒素中毒治疗策略提供了可能。
Ricin is one of a group of structurally related plant lectins and is extractedGroups of rats were exposed to ricin aerosol by inhalation, total LCt(1) = 11.21 mg.min.m(-3) (an approximate LCt(30) exposure) and examined, using transmission electron microscopy, at intervals up to 48 h after exposure.The first signs of change in ultrastructure were seen at between 6 and 12 h post exposure in alveolar macrophages and took the form of apoptotic changes primarily in the nucleus. These included heterochromatin condensation at the nuclear periphery and crenulation of the nuclear membrane. There then followed a sequence of changes in the cells of the alveolar wall and blood/air barrier culminating in intra-alveolar oedema at 12 and 15 h after exposure.Damage was first observed in the capillary endothelium and type I epithelial cell changes were evident from 12 h post exposure onward. These changes appeared to be necrotic rather than apoptotic in nature and suggest that mechanisms other than a direct effect of ricin may be involved.Associated with these changes were mixed inflammatory cell infiltrates in the interstitium, isolated type II pneumocyte necrosis and evidence of microvascular microthrombosis. By 48 h after exposure, the intra-alveolar oedema appeared less marked with prominent hyperplasia of type II pneumocytes.The identification that apoptosis of alveolar macrophages plays a significant part in the mechanism of toxicity following exposure to ricin raises the possibility of developing new therapeutic strategies against poisoning by ricin.