B. anthracis edema toxin increases cAMP levels and inhibits phenylephrine-stimulated contraction in a rat aortic ring model.
B. anthracis edema toxin increases cAMP levels and inhibits phenylephrine-stimulated contraction in a rat aortic ring model.
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DOI：
10.1152/ajpheart.00185.2013
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发表时间：
2013-07
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影响因子：
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通讯作者：
Yan Li;X. Cui;Steven B. Solomon;Kenneth E. Remy;Y. Fitz;P. Eichacker
中科院分区：
文献类型：
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作者：
Yan Li;X. Cui;Steven B. Solomon;Kenneth E. Remy;Y. Fitz;P. Eichacker
B。炭疽水肿毒素（ET）和致死毒素（LT）均由宿主细胞摄取毒素所必需的保护性抗原（PA）及其各自的毒性部分水肿因子（EF）和致死因子（LF）组成。虽然这两种毒素都可能导致感染期间的休克，但其机制尚不清楚。为了测试ET和LT是否产生动脉舒张，在Sprague-Dawley大鼠主动脉环模型中测量它们对苯肾上腺素（PE）刺激的收缩的作用。制备环并将其连接至压力传感器。证实了它们的活力，并测定了60 mM KCl的峰值收缩。与PA预处理相比（对照，60分钟），ET预处理浓度与体内观察到的相似，降低了平均（±SE）最大收缩力（MCF;峰值收缩百分比）（96.2 ± 7.0 vs. 57.3 ± 9.1），并增加产生一半MCF的估计PE浓度（EC 50; 10（-7）M，1.1 ± 0.3 vs. 3.7 ± 0.8，P ≤ 0.002）。PA单克隆抗体抑制ET、阿德福韦酯选择性抑制EF或去除环内皮可抑制ET对MCF和EC 50的影响（P ≤ 0.02）。与其腺苷酸环化酶活性一致，ET增加了内皮完整但内皮剥脱环中的组织cAMP（P 0.05）。在PE预收缩的环中，与PA后处理（90分钟）相比，ET后处理使内皮完整的环的收缩力进行性降低，舒张力增加（P < 0.0001），但不影响内皮剥脱的环（P = 0.51）。因此，ET可能通过产生动脉舒张而导致休克。
B. anthracis edema toxin (ET) and lethal toxin (LT) are each composed of protective antigen (PA), necessary for toxin uptake by host cells, and their respective toxic moieties, edema factor (EF) and lethal factor (LF). Although both toxins likely contribute to shock during infection, their mechanisms are unclear. To test whether ET and LT produce arterial relaxation, their effects on phenylephrine (PE)-stimulated contraction in a Sprague-Dawley rat aortic ring model were measured. Rings were prepared and connected to pressure transducers. Their viability was confirmed, and peak contraction with 60 mM KCl was determined. Compared with PA pretreatment (control, 60 min), ET pretreatment at concentrations similar to those noted in vivo decreased the mean (±SE) maximum contractile force (MCF; percent peak contraction) in rings generated during stimulation with increasing PE concentrations (96.2 ± 7.0 vs. 57.3 ± 9.1) and increased the estimated PE concentration producing half the MCF (EC50; 10(-7) M, 1.1 ± 0.3 vs. 3.7 ± 0.8, P ≤ 0.002). ET inhibition with PA-directed monoclonal antibodies, selective EF inhibition with adefovir, or removal of the ring endothelium inhibited the effects of ET on MCF and EC50 (P ≤ 0.02). Consistent with its adenyl cyclase activity, ET increased tissue cAMP in endothelium-intact but not endothelium-denuded rings (P 0.05). In rings precontracted with PE compared with posttreatment with PA (90 min), ET posttreatment produced progressive reductions in contractile force and increases in relaxation in endothelium-intact rings (P < 0.0001) but not endothelium-denuded rings (P = 0.51). Thus, ET may contribute to shock by producing arterial relaxation.