Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China. lqsongxian @ gmail.com
Int Arch Allergy Immunol. 2013;161(3):243-51. doi: 10.1159/000345972. Epub 2013 Mar 15.
Calcium-activated chloride channels (CLCAs) have been found to be preferentially expressed on the secretory epithelium. They may play a pivotal role in mucous overproduction by bronchial goblet cells in asthma. It has been reported that the inhibition of CLCAs with niflumic acid could relieve the symptoms of asthma. However, niflumic acid has serious adverse effects. DNA vaccination is considered to be a promising strategy to treat allergic diseases such as asthma and dust mite allergy.
We constructed a vaccine encoding human CLCA1 (hCLCA1) and evaluated its effects on promoting antibodies against hCLCA1 and the related preventive function in a mouse model of asthma.
Our results reveal that the induced hCLCA1 antibodies can be detected in the first 2 weeks after immunization with hCLCA1 plasmids (hCLCA1-p) by intramuscular injection and augmented gradually in the following several weeks. The autoantibodies against hCLCA1 induced by the DNA vaccine bound to three segments of the mouse CLCA3 (mCLCA3) protein, including the amino terminal (PepN), the carboxyl terminal (PepC) and the middle of the protein (PepM). In our study, mice immunized with hCLCA1-p developed fewer pathological changes compared with other control groups, including a remarkable reduction in the air pressure-time index of the trachea, the number of eosinophils and mast cells in the bronchoalveolar lavage fluid and the mRNA level of MUC5AC in goblet cells.
Taken together, our results suggest that a DNA vaccine encoding the CLCA protein may have potential as a useful pharmacotherapy for asthma in the future.
钙激活氯离子通道（CLCA）被发现优先表达于分泌上皮细胞。它们可能在哮喘时支气管杯状细胞的黏液过度产生中发挥关键作用。已有报道称，使用尼氟酸抑制 CLCA 可缓解哮喘症状。然而，尼氟酸具有严重的不良反应。DNA 疫苗被认为是治疗哮喘和尘螨过敏等过敏性疾病的一种有前途的策略。
我们构建了编码人 CLCA1（hCLCA1）的疫苗，并评估了其在促进针对 hCLCA1 的抗体产生及其在哮喘小鼠模型中的相关预防功能方面的效果。
我们的结果表明，通过肌肉内注射 hCLCA1 质粒（hCLCA1-p）进行免疫后，在第 2 周内即可检测到诱导的 hCLCA1 抗体，并在随后的几周内逐渐增加。该 DNA 疫苗诱导的针对 hCLCA1 的自身抗体与 mouse CLCA3（mCLCA3）蛋白的三个片段结合，包括氨基端（PepN）、羧基端（PepC）和蛋白的中部（PepM）。在我们的研究中，与其他对照组相比，用 hCLCA1-p 免疫的小鼠发生的病理变化较少，包括气管的压力-时间指数显著降低、支气管肺泡灌洗液中的嗜酸性粒细胞和肥大细胞数量减少以及杯状细胞中 MUC5AC 的 mRNA 水平降低。
综上所述，我们的结果表明，编码 CLCA 蛋白的 DNA 疫苗可能具有作为未来哮喘有用药物治疗的潜力。
