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首页> 外文期刊>Allergy >Inhibition of extracellular nucleotides hydrolysis intensifies the allergic bronchospasm. A novel protective role of ectonucleotidases
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Inhibition of extracellular nucleotides hydrolysis intensifies the allergic bronchospasm. A novel protective role of ectonucleotidases

机译：抑制细胞外核苷酸水解会加剧过敏性支气管痉挛。胞外核苷酸酶的新型保护作用

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Background: Nucleotides released to the extracellular space stimulate purinergic receptors, and their effects are modulated by ectonucleotidases. The role of ATP in the allergic bronchospasm has been scantly studied. Methods: We used several techniques (plethysmography, organ baths, confocal microscopy, RT-PCR, ATP measurement) to explore the role of nucleotides and ectonucleotidases in the allergic bronchospasm in guinea pigs. Results: While allergenic challenge with a low-dose ovalbumin (OVA) only produced a small bronchospasm (～2-fold the basal lung resistance), previous inhibition of ectonucleotidases by ARL-67156 greatly intensified this response (～11-fold the basal lung resistance, with 44% mortality). Bronchoalveolar lavage fluid obtained during this bronchospasm contained increased ATP concentration. This potentiation was abolished by antagonism of purinergic receptors (suramin+RB2) or TXA2 receptor (SQ29548), or by intratracheal apyrase. In tracheal rings and lung parenchyma strips, OVA caused a concentration-dependent contraction. Suramin+RB2 or levamisole produced a significant rightward displacement of this response, and ARL-67156 did not modify it. Platelets stimulated with OVA released ATP. Confocal images of nonsensitized tracheas showed slight fluorescence for P2Y6 receptors in epithelium and none for P2Y4. Sensitized animals showed strong fluorescence to both receptors and to alkaline phosphatase in the airway epithelium. This correlated with a large increment in mRNA for P2Y4 and P2Y6 receptors in sensitized animals. Conclusions: Nucleotides greatly potentiate the allergic bronchospasm when ectonucleotidases activity is diminished, and this effect is probably favored by the upregulation of P2Y4 and P2Y6 receptors in airway epithelium during sensitization. These results prompt for further research on these mechanisms in human asthma.
机译：背景：释放到细胞外空间的核苷酸刺激嘌呤能受体，其作用受到外切核苷酸酶的调节。 ATP在过敏性支气管痉挛中的作用已很少研究。方法：我们使用了几种技术（体积描记法，器官浴，共聚焦显微镜，RT-PCR，ATP测量）来探讨核苷酸和外切核苷酸酶在豚鼠过敏性支气管痉挛中的作用。结果：低剂量卵清蛋白（OVA）致敏刺激仅产生细支气管痉挛（基础肺抵抗力的2倍），而先前ARL-67156对外切核苷酸酶的抑制作用极大地增强了这种反应（基础肺约为11倍）抵抗，死亡率为44％）。在此支气管痉挛过程中获得的支气管肺泡灌洗液含有增加的ATP浓度。嘌呤能受体（suramin + RB2）或TXA2受体（SQ29548）的拮抗作用或气管内的腺苷三磷酸双磷酸酶消除了这种增强作用。在气管环和肺实质薄带中，OVA引起浓度依赖性收缩。 Suramin + RB2或左旋咪唑使该反应明显向右移位，而ARL-67156并未对其进行修饰。用OVA刺激的血小板释放ATP。未敏化气管的共聚焦图像显示上皮中P2Y6受体的荧光很小，而P2Y4则无荧光。致敏的动物对气道上皮中的受体和碱性磷酸酶均显示强荧光。这与致敏动物中P2Y4和P2Y6受体的mRNA大量增加有关。结论：当核苷酸外切酶活性降低时，核苷酸可大大增强过敏性支气管痉挛，敏化过程中气道上皮细胞中P2Y4和P2Y6受体的上调可能促进了这种作用。这些结果促使人们进一步研究人类哮喘中的这些机制。

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