Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Epidemiological Department, Huadong Medical Institute of Biotechniques, Nanjing, Jiangsu 210002, China.
Chin Med J (Engl). 2021 Feb 16;134(7):757-764. doi: 10.1097/CM9.0000000000001381.
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.
慢性阻塞性肺疾病（COPD）已成为全球第三大致死原因，给医疗保健系统带来了沉重的经济负担。慢性支气管炎是导致 COPD 的最常见疾病，无论是在局部还是全身性。中性粒细胞炎症在 COPD 气道壁和管腔中占主导地位。从逻辑上讲，抑制中性粒细胞增多是 COPD 治疗的重要方式。然而，目前可用的抗中性粒细胞疗法对 COPD 患者几乎没有益处，并且可能有严重的副作用。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 在人类中性粒细胞和单核细胞上高度表达。通过化学化合物或合成配体与 Siglec-9 的结合，诱导人类中性粒细胞凋亡和自噬样细胞死亡。此外，在体内气道炎症的小鼠模型中，给予 Siglec-E（Siglec-9 的小鼠功能同源物）抗体可抑制中性粒细胞的募集和激活。鉴于中性粒细胞在慢性支气管炎和肺气肿中的关键作用，针对 Siglec-9 可能有益于 COPD、哮喘、纤维化和相关慢性炎症性肺部疾病的治疗。
