Sánchez-Monsálvez I, De Armas-Serrá C, Bernadina W, Rodríguez-Caabeiro F
Laboratorio de Parasitología, Facultad de Farmacia, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
Dig Dis Sci. 2003 Dec;48(12):2342-52. doi: 10.1023/b:ddas.0000007873.48287.f6.
Anisakis simplex IgE may bring on allergic responses such as angioedema, vomiting, and urticaria from eating seafood, but it is not the only etiology. Induced cholinergic hyperreactivity or adrenergic blockade in the target tissue can cause these diseases nonimmunologically also. Here we studied the effects on normal intestinal motility of brief A. simplex infections and in vitro exposures to the parasite's extract (CE). Each approach was evaluated according to its ability to induce cholinergic hyperreactivity or adrenergic blockade in rat duodenum (RD), jejunum (RJ), and ileum (RI) in vitro. Additionally, bolus propulsion in RD, RJ, and RI was evaluated with time in vivo utilizing animals infected 4 h previously with A. simplex larvae (L3) vs sham animals. Tissues, after inoculation of 1, 5, 10, and 20 L3, exhibited time- and dose-dependent motility changes after carbachol (Ch) and noradrenaline (NA), justifying our using herein rats from the fourth hour of infection with 20 L3. We observed a persistent, yet differential effect of the infection on RD, RJ, and RI responses to Ch or NA. It caused cholinergic (muscarinic) hyperreactivity in RD only, and adrenergic blockade in all other parts, and consequently increased the transit index in RD, not in RJ or RI. In contrast, exposing RD, RJ, and RI to CE persistently increased both parameters, amplitude of twitches and muscular tone, in all, albeit that, here also, responses to Ch and NA were CE dose dependent. Interestingly, sensitivity to CE was in the order RI > RJ > RD, the reverse situation of that observed during active infection. Thus, previously viable A. simplex L3, after digestion, can exert bystander disturbance in autonomic control in the whole intestine. Our findings demonstrate that A. simplex L3, alive or dead, can induce cholinergic hyperactivity and adrenergic blockade in the whole small intestine and, as a consequence, gastrointestinal symptoms. Significantly, they may do so long before parasite-specific IgE is detectably induced or despite the occurrence of such IgE.
简单异尖线虫IgE可能会引发诸如血管性水肿、呕吐和食用海鲜后出现荨麻疹等过敏反应,但它并非唯一病因。靶组织中诱导的胆碱能反应性亢进或肾上腺素能阻滞也可非免疫性地导致这些疾病。在此,我们研究了短暂的简单异尖线虫感染以及体外暴露于该寄生虫提取物(CE)对正常肠道运动的影响。每种方法都根据其在体外诱导大鼠十二指肠(RD)、空肠(RJ)和回肠(RI)中胆碱能反应性亢进或肾上腺素能阻滞的能力进行评估。此外,利用4小时前感染简单异尖线虫幼虫(L3)的动物与假手术动物,在体内随时间评估RD、RJ和RI中的团块推进情况。接种1、5、10和20条L3后,组织在卡巴胆碱(Ch)和去甲肾上腺素(NA)作用下表现出时间和剂量依赖性的运动变化,这证明我们在此使用感染20条L3后第4小时的大鼠是合理的。我们观察到感染对RD、RJ和RI对Ch或NA的反应具有持续但不同的影响。它仅在RD中引起胆碱能(毒蕈碱型)反应性亢进,而在所有其他部位引起肾上腺素能阻滞,因此增加了RD中的转运指数,而RJ或RI中则未增加。相比之下,将RD、RJ和RI暴露于CE会持续增加所有部位的两个参数,即抽搐幅度和肌张力,尽管在此处对Ch和NA的反应也依赖于CE剂量。有趣的是,对CE的敏感性顺序为RI > RJ > RD,这与在活跃感染期间观察到的情况相反。因此,先前存活的简单异尖线虫L3在消化后可对整个肠道的自主控制产生旁观者干扰。我们的研究结果表明,活的或死的简单异尖线虫L3均可在整个小肠中诱导胆碱能亢进和肾上腺素能阻滞,并因此导致胃肠道症状。重要的是,它们可能早在可检测到寄生虫特异性IgE诱导之前或尽管出现了这种IgE就会这样做。