Zhang Junxian, Yang Xin, Xu Xingmeng, Shen Qinhao, Han Fei, Zhu Qingtian, Wu Keyan, Gu Aidong, Wu Dong, Xiao Weiming
Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225000, China.
Operating Room of Anesthesia Surgery Center, West China Hospital, West China School of Nursing, Sichuan University, Chengdu 610041, China.
J Clin Med. 2023 Mar 27;12(7):2533. doi: 10.3390/jcm12072533.
The inflammatory immune response mediated by neutrophils is closely related to the progression of acute pancreatitis. Previous studies confirmed that CD177 is a neutrophil-specific marker involved in the pathogenesis of conditions such as systemic vasculitis, asthma, and polycythemia vera. Neutrophil extracellular trap (NET) formation is a specific death program by which neutrophils release nuclear DNA covered with histones, granule proteins, etc. It also plays an important role in host defense and various pathological reactions. However, the function of CD177 in regulating the generation of NETs and the development of acute pancreatitis (AP) is unclear. In our manuscript, CD177 was significantly elevated in blood neutrophils in patients and positively correlated with the AP disease severity. Then, recombinant human CD177 protein (rhCD177) could significantly improve pancreatic injury and the inflammatory response in AP mice, and reduce AP-related lung injury. Mechanistically, we found that rhCD177 could inhibit the formation of NETs by reducing reactive oxygen species (ROS) and myeloperoxidase (MPO)/citrullinated histone H3 (CitH3) release. For the first time, we discovered the potential of rhCD177 to protect AP in mice and inhibit the NET formation of AP. CD177 may be a potential treatment strategy for preventing or inhibiting the aggravation of AP.
中性粒细胞介导的炎症免疫反应与急性胰腺炎的进展密切相关。先前的研究证实，CD177是一种中性粒细胞特异性标志物，参与系统性血管炎、哮喘和真性红细胞增多症等疾病的发病机制。中性粒细胞胞外陷阱（NET）形成是一种特殊的死亡程序，中性粒细胞通过该程序释放覆盖有组蛋白、颗粒蛋白等的核DNA。它在宿主防御和各种病理反应中也起着重要作用。然而，CD177在调节NETs生成和急性胰腺炎（AP）发展中的功能尚不清楚。在我们的论文中，患者血液中的中性粒细胞中CD177显著升高，且与AP疾病严重程度呈正相关。然后，重组人CD177蛋白（rhCD177）可显著改善AP小鼠的胰腺损伤和炎症反应，并减轻AP相关的肺损伤。机制上，我们发现rhCD177可通过减少活性氧（ROS）和髓过氧化物酶（MPO）/瓜氨酸化组蛋白H3（CitH3）的释放来抑制NETs的形成。我们首次发现rhCD177在保护小鼠AP和抑制AP的NET形成方面的潜力。CD177可能是预防或抑制AP加重的一种潜在治疗策略。
