Xu Liangyu, Wei Zichen, Wu Rongfang, Kong Siqi, Bin Jinlian, Gao Yuxin, Fang Lei
Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, China.
Pathology Department, Dongtai Hospital of Traditional Chinese Medicine, Yancheng, China.
Front Allergy. 2025 Jun 3;6:1594028. doi: 10.3389/falgy.2025.1594028. eCollection 2025.
Ovalbumin (OVA) and house dust mite (HDM) are widely used allergenic proteins in murine models of allergic asthma. In our previous studies, shrimp tropomyosin (ST) was shown to induce type I hypersensitivity, including asthma-like responses. Here, we compared airway eosinophilic inflammation models induced by OVA, HDM, or ST using a protocol of three intraperitoneal (i.p.) sensitizations followed by a single intratracheal (i.t.) allergen challenge.
C57BL/6J mice were sensitized via three i.p. injections of OVA, HDM, or ST mixed with Al(OH), followed by a single i.t. challenge with the respective allergen. Lung transcriptomic analysis, plasma IgE levels, bronchoalveolar lavage (BAL) fluid cell counts, cytokine and chemokine mRNA levels, and histopathological assessments were performed to evaluate airway inflammation.
A single i.t. challenge with ST or HDM significantly increased the lung-to-body weight ratio, eosinophil infiltration, and mucus hypersecretion, accompanied by elevated mRNA levels of Th2 cytokines (, , ) and increased the total cell count and eosinophil count in the BAL fluid. In contrast, OVA induced only mild eosinophilic inflammation, suggesting that repeated exposures may be required to elicit a robust allergic response. RNA sequencing and qRT-PCR further identified key chemokines associated with eosinophil recruitment (, ), Th2 polarization (), and neutrophil activation ().
A single i.t. challenge of ST, similar to HDM, exhibits a potent ability to induce eosinophilic inflammation and Th2-type immune responses in a murine model of allergic asthma, surpassing the effects of OVA.
卵清蛋白（OVA）和屋尘螨（HDM）是变应性哮喘小鼠模型中广泛使用的变应原性蛋白。在我们之前的研究中，虾原肌球蛋白（ST）被证明可诱导I型超敏反应，包括哮喘样反应。在此，我们使用三次腹腔内（i.p.）致敏，随后单次气管内（i.t.）给予变应原激发的方案，比较了由OVA、HDM或ST诱导的气道嗜酸性粒细胞炎症模型。
通过三次腹腔内注射OVA、HDM或与氢氧化铝混合的ST对C57BL/6J小鼠进行致敏，随后用相应变应原进行单次气管内激发。进行肺转录组分析、血浆IgE水平测定、支气管肺泡灌洗（BAL）液细胞计数、细胞因子和趋化因子mRNA水平测定以及组织病理学评估，以评估气道炎症。
单次气管内给予ST或HDM激发显著增加了肺与体重之比、嗜酸性粒细胞浸润和黏液分泌亢进，同时伴有Th2细胞因子（ 、 、 ）mRNA水平升高，并增加了BAL液中的总细胞计数和嗜酸性粒细胞计数。相比之下，OVA仅诱导了轻度嗜酸性粒细胞炎症，这表明可能需要反复接触才能引发强烈的变应性反应。RNA测序和qRT-PCR进一步鉴定了与嗜酸性粒细胞募集（ 、 ）、Th2极化（ ）和中性粒细胞活化（ ）相关的关键趋化因子。
与HDM相似，单次气管内给予ST在变应性哮喘小鼠模型中具有诱导嗜酸性粒细胞炎症和Th2型免疫反应的强大能力，超过了OVA的作用。
