CD177 Inhibits Neutrophil Extracellular Trap Formation and Protects against Acute Pancreatitis in Mice

• Published in: Journal of clinical medicine Vol. 12; no. 7; p. 2533
• Main Authors: Zhang, Junxian, Yang, Xin, Xu, Xingmeng, Shen, Qinhao, Han, Fei, Zhu, Qingtian, Wu, Keyan, Gu, Aidong, Wu, Dong, Xiao, Weiming
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.03.2023; MDPI
• Subjects: acute pancreatitis; Analysis; Antibodies; Antigens; Care and treatment; Clinical medicine; Cloning; Diagnosis; Enzymes; Flow cytometry; Histones; Immune response; Inflammatory diseases; Laboratory animals; Multiple organ dysfunction syndrome; Multiple organ failure; neutrophil extracellular trap; Neutrophils; Pancreatitis; pathogenesis; Pathogens; Prevention; reactive oxygen species; Risk factors; Tumor necrosis factor-TNF; China; United States > US; Japan; pathogenesis; acute pancreatitis; reactive oxygen species; neutrophil extracellular trap
• ISSN: 2077-0383; 2077-0383
• 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.