Bacillus anthracis edema toxin causes extensive tissue lesions and rapid lethality in mice
Bacillus anthracis edema toxin causes extensive tissue lesions and rapid lethality in mice
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DOI：
10.1016/s0002-9440(10)61218-7
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发表时间：
2005-11-01
影响因子：
6
通讯作者：
Leppla, SH
中科院分区：
文献类型：
--
作者：
Firoved, AM;Miller, GF;Leppla, SH
炭疽芽孢杆菌水肿性毒素是一种腺酰环化酶，是炭疽病的重要致病因子。然而，ET在炭疽发病机制中的作用却知之甚少。以前使用与皮下水肿相关的粗毒素制剂和缺乏ET的炭疽杆菌菌株的研究表明，毒力降低。我们报道了首次在动物模型中对ET诱导的病理学进行的全面研究。高纯度的ET在较低剂量下导致BALB/CJ小鼠死亡，比以前看到的另一种主要炭疽杆菌毒力因子--致命毒素--更快。大体病理观察显示肠腔内积液，随后回肠和肾上腺局灶性出血。对定时采集的组织进行的组织病理学分析显示，包括肾上腺、淋巴器官、骨、骨髓、胃肠粘膜、心脏和肾脏在内的几个组织都有病变。伴随而来的血液化学分析支持组织损伤的诱导。ET治疗后多种细胞因子升高，包括粒细胞集落刺激因子、嗜酸性粒细胞趋化因子、角质形成细胞衍生细胞因子、单核细胞趋化蛋白1/JE、白介素6、白介素10和白介素1β。生理测量也显示同时存在低血压和心动过缓。这些研究详细说明了ET引起的广泛病理损害，并提示它可导致多器官衰竭而死亡。
Bacillus anthracis edema toxin (ET), an adenylyl cyclase, is an important virulence factor that contributes to anthrax disease. The role of ET in anthrax pathogenesis is, however, poorly understood. Previous studies using crude toxin preparations associated ET with subcutaneous edema, and ET-deficient strains of B. anthracis showed a reduction in virulence. We report the first comprehensive study of ET-induced pathology in an animal model. Highly purified ET caused death in BALB/cJ mice at lower doses and more rapidly than previously seen with the other major B. anthracis virulence factor, lethal toxin. Observations of gross pathology showed intestinal intralumenal fluid accumulation followed by focal hemorrhaging of the ileum and adrenal glands. Histopathological analyses of timed tissue harvests revealed lesions in several tissues including adrenal glands, lymphoid organs, bone, bone marrow, gastrointestinal mucosa, heart, and kidneys. Concomitant blood chemistry analyses supported the induction of tissue damage. Several cytokines increased after ET administration, including granulocyte colony-stimulating factor, eotaxin, keratinocyte-derived cytokine, MCP-1/JE, interleukin-6, interleukin-10, and interleukin-1 beta. Physiological measurements also revealed a concurrent hypotension and bradycardia. These studies detail the extensive pathological lesions caused by ET and suggest that it causes death due to multiorgan failure.