Sialic acid-binding immunoglobulin-like lectin 9 as a potential therapeutic target for chronic obstructive pulmonary disease.
Sialic acid-binding immunoglobulin-like lectin 9 as a potential therapeutic target for chronic obstructive pulmonary disease.
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DOI：
10.1097/cm9.0000000000001381
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发表时间：
2021-02-16
影响因子：
6.1
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Chen Z;Xu SL;Ge LY;Zhu J;Zheng T;Zhu Z;Zhou L
慢性阻塞性肺疾病(COPD)已成为全球第三大死亡原因，给医疗保健系统带来了严重的经济负担。慢性支气管炎是导致COPD的最常见的疾病，无论是局部的还是全身的。中性粒细胞炎症主要见于COPD气道壁和管腔。从逻辑上讲，抑制中性粒细胞增多是COPD治疗的一种基本方式。然而，目前可用的抗中性粒细胞疗法对COPD患者几乎没有好处，可能会有严重的副作用。因此，迫切需要探索一种有效且安全的抗中性粒细胞治疗方法，以延缓疾病的进展。唾液酸结合免疫球蛋白样凝集素(Siglec)-9是Siglec细胞表面免疫球蛋白家族的成员。值得注意的是，Siglec-9在人中性粒细胞和单核细胞上高度表达。化合物或合成配体连接Siglec-9诱导人中性粒细胞凋亡和自噬样细胞死亡。此外，给予Siglec-E的抗体，Siglec-9的小鼠功能同系物，在体内的小鼠呼吸道炎症模型中抑制中性粒细胞的招募和激活。鉴于中性粒细胞在慢性支气管炎和肺气肿中的关键作用，靶向Siglec-9可能有助于COPD、哮喘、纤维化和相关的慢性炎症性肺部疾病的治疗。
Chronic obstructive pulmonary disease (COPD) has become the third-leading cause of death worldwide, which is a severe economic burden to the healthcare system. Chronic bronchitis is the most common condition that contributes to COPD, both locally and systemically. Neutrophilic inflammation predominates in the COPD airway wall and lumen. Logically, repression of neutrophilia is an essential fashion to COPD treatment. However, currently available anti-neutrophilic therapies provide little benefit in COPD patients and may have serious side effects. Thus, there is an urgent need to explore an effective and safe anti-neutrophilic approach that might delay progression of the disease. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9 is a member of the Siglec cell surface immunoglobulin family. It is noteworthy that Siglec-9 is highly expressed on human neutrophils and monocytes. Ligation of Siglec-9 by chemical compounds or synthetic ligands induced apoptosis and autophagic-like cell death in human neutrophils. Furthermore, administration of antibody to Siglec-E, mouse functional ortholog of Siglec-9, restrained recruitment and activation of neutrophils in mouse models of airway inflammation in vivo. Given the critical role that neutrophils play in chronic bronchitis and emphysema, targeting Siglec-9 could be beneficial for the treatment of COPD, asthma, fibrosis, and related chronic inflammatory lung diseases.