Sim Soyoon, Yang Eun-Mi, Shin Yoo Seob, Kim Seon Beom, Choi Youngwoo, Park Hae-Sim
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
Department of Food Science and Technology, Pusan National University, Miryang, Korea.
Clin Transl Allergy. 2025 Jul;15(7):e70077. doi: 10.1002/clt2.70077.
Eotaxins (EOTs), primarily expressed in airway epithelial cells (AECs), act as chemoattractants for eosinophils in asthma pathogenesis. Recent studies have suggested that EOTs have additional functions beyond chemotaxis. However, the distinct roles of EOTs remain incompletely understood.
Serum EOT1, EOT2, myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were evaluated by ELISA and serum eosinophil cationic protein (ECP) levels were measured by ImmunoCAP in 79 adult asthmatics. Clinical characteristics were analyzed by inflammatory phenotype, disease severity, and serum EOT1/EOT2 levels. The functions of EOTs were investigated in vitro and ex vivo. For in vivo, EOT1 and EOT2 were intranasally administered to ovalbumin/lipopolysaccharide-induced asthmatic mice (BALB/c). To assess neutralization effects, anti-EOT1 or anti-EOT2 antibodies were intranasally administered.
Serum EOT1 and EOT2 levels were higher in patients with severe asthma (SA) than in those with non-SA. Serum EOT1 levels were associated with increased blood/sputum eosinophil counts and serum ECP levels, but not significantly correlated with FEV (%) values. In contrast, serum EOT2 levels are correlated with higher serum MPO, MMP-9, and TIMP-1 levels but lower FEV (%). In asthmatic mice, EOT1 increased eosinophil counts and IL-5 production, whereas EOT2 induced CXCL1 and MMP-9 production, junctional dysfunction and epithelial-to-mesenchymal transition in the lungs, which were attenuated by neutralizing EOTs using each antibody.
EOT1 promotes T2/eosinophilic inflammation, whereas EOT2 accelerates airway remodeling and lung function decline by activating neutrophils, providing a new insight into the distinct roles of EOTs in the pathogenesis of SA.
嗜酸性粒细胞趋化因子（EOTs）主要在气道上皮细胞（AECs）中表达，在哮喘发病机制中作为嗜酸性粒细胞的趋化因子。最近的研究表明，EOTs除了趋化作用外还有其他功能。然而，EOTs的不同作用仍未完全了解。
通过酶联免疫吸附测定（ELISA）评估79例成年哮喘患者血清中EOT1、EOT2、髓过氧化物酶（MPO）、基质金属蛋白酶-9（MMP-9）和金属蛋白酶组织抑制剂-1（TIMP-1）水平，通过免疫化学发光法（ImmunoCAP）测定血清嗜酸性粒细胞阳离子蛋白（ECP）水平。根据炎症表型、疾病严重程度和血清EOT1/EOT2水平分析临床特征。在体外和体内研究EOTs的功能。在体内，将EOT1和EOT2经鼻给予卵清蛋白/脂多糖诱导的哮喘小鼠（BALB/c）。为评估中和作用，经鼻给予抗EOT1或抗EOT2抗体。
重度哮喘（SA）患者血清EOT1和EOT2水平高于非SA患者。血清EOT1水平与血液/痰液嗜酸性粒细胞计数增加和血清ECP水平相关，但与第1秒用力呼气容积（FEV₁%）值无显著相关性。相反，血清EOT2水平与较高的血清MPO、MMP-9和TIMP-1水平相关，但与较低的FEV₁%相关。在哮喘小鼠中，EOTI增加嗜酸性粒细胞计数和白细胞介素-5（IL-5）产生，而EOT2诱导肺中CXC趋化因子配体1（CXCL1）和MMP-9产生、连接功能障碍和上皮-间质转化，使用每种抗体中和EOTs可使其减弱。
EOT1促进2型/嗜酸性粒细胞炎症，而EOT2通过激活中性粒细胞加速气道重塑和肺功能下降，为EOTs在SA发病机制中的不同作用提供了新见解。
