{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:40:54Z","timestamp":1790829654448,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation","award":["32170788"],"award-info":[{"award-number":["32170788"]}]},{"name":"National Natural Science Foundation","award":["YZ2022080"],"award-info":[{"award-number":["YZ2022080"]}]},{"name":"Yangzhou Key Research and Development Program (Social Development) Project","award":["32170788"],"award-info":[{"award-number":["32170788"]}]},{"name":"Yangzhou Key Research and Development Program (Social Development) Project","award":["YZ2022080"],"award-info":[{"award-number":["YZ2022080"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/jcm12072533","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T01:41:34Z","timestamp":1679967694000},"page":"2533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["CD177 Inhibits Neutrophil Extracellular Trap Formation and Protects against Acute Pancreatitis in Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Junxian","family":"Zhang","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Operating Room of Anesthesia Surgery Center, West China Hospital, West China School of Nursing, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingmeng","family":"Xu","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhao","family":"Shen","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Han","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingtian","family":"Zhu","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyan","family":"Wu","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidong","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Xiao","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.3892\/mmr.2016.5008","article-title":"Cathelicidin-related antimicrobial peptide modulates the severity of acute pancreatitis in mice","volume":"13","author":"Deng","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_2","first-page":"854","article-title":"Portosplenomesenteric venous thrombosis in patients with acute pancreatitis is associated with pancreatic necrosis and usually has a benign course","volume":"12","author":"Easler","year":"2014","journal-title":"Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1038\/ajg.2013.218","article-title":"American College of Gastroenterology Guideline: Management of Acute Pancreatitis","volume":"108","author":"Tenner","year":"2013","journal-title":"Am. J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.biocel.2005.12.001","article-title":"Pancreatic acinar cell: Its role in acute pancreatitis","volume":"38","author":"Leung","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1136\/gutjnl-2012-302779","article-title":"Classification of acute pancreatitis\u20142012: Revision of the Atlanta classification and definitions by international consensus","volume":"62","author":"Banks","year":"2013","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"351","DOI":"10.5152\/tjg.2014.13005","article-title":"Pathophysiology, classification and available guidelines of acute pancreatitis","volume":"25","author":"Ince","year":"2014","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1136\/gutjnl-2017-314657","article-title":"Impact of characteristics of organ failure and infected necrosis on mortality in necrotising pancreatitis","volume":"68","author":"Schepers","year":"2019","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1016\/S0140-6736(17)32129-3","article-title":"Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults","volume":"390","author":"Abdeen","year":"2017","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41575-018-0087-5","article-title":"Global epidemiology and holistic prevention of pancreatitis","volume":"16","author":"Petrov","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil Extracellular Traps Kill Bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11850","DOI":"10.1002\/jcp.27874","article-title":"Targeting peptidylarginine deiminase reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis","volume":"234","author":"Madhi","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1479-5876-2-8","article-title":"CD177: A member of the Ly-6 gene superfamily involved with neutrophil proliferation and polycythemia vera","volume":"2","author":"Stroncek","year":"2004","journal-title":"J. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1365-2141.2004.05027.x","article-title":"Neutrophil CD177 (NB1 gp, HNA-2a) expression is increased in severe bacterial infections and polycythaemia vera","volume":"126","author":"Wolff","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1002\/art.24442","article-title":"Coexpression of CD177 and membrane proteinase 3 on neutrophils in antineutrophil cytoplasmic autoantibody-associated systemic vasculitis: Anti-proteinase 3-mediated neutrophil activation is independent of the role of CD177-expressing neutrophils","volume":"60","author":"Hu","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1084\/jem.20092253","article-title":"Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis","volume":"207","author":"Feng","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1136\/gutjnl-2015-310374","article-title":"IL-36R signalling activates intestinal epithelial cells and fibroblasts and promotes mucosal healing in vivo","volume":"66","author":"Scheibe","year":"2017","journal-title":"Gut"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1002\/eji.201546160","article-title":"Commensal A4 bacteria inhibit intestinal Th2-cell responses through induction of dendritic cell TGF-\u03b2 production","volume":"46","author":"Wu","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7222","DOI":"10.3748\/wjg.v19.i42.7222","article-title":"Animal models of pancreatitis: Can it be translated to human pain study?","volume":"19","author":"Zhao","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4187398","DOI":"10.1155\/2021\/4187398","article-title":"CaMK II Inhibition Attenuates ROS Dependent Necroptosis in Acinar Cells and Protects against Acute Pancreatitis in Mice","volume":"2021","author":"Zhu","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s00534-005-1047-3","article-title":"JPN Guidelines for the management of acute pancreatitis: Epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis","volume":"13","author":"Sekimoto","year":"2006","journal-title":"J. Hepato-Biliary-Pancreat. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1445-1433.2004.02940.x","article-title":"Trends in the management of severe acute pancreatitis: Interventions and outcome","volume":"74","author":"Flint","year":"2004","journal-title":"ANZ J. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.2147\/JHC.S303588","article-title":"The Crosstalk between Cancer Cells and Neutrophils Enhances Hepatocellular Carcinoma Metastasis via Neutrophil Extracellular Traps-Associated Cathepsin G Component: A Potential Therapeutic Target","volume":"8","author":"Guan","year":"2021","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1097\/00075198-200204000-00012","article-title":"Lung injury in acute pancreatitis: Mechanisms, prevention, and therapy","volume":"8","author":"Shields","year":"2002","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1053\/j.gastro.2015.08.026","article-title":"Neutrophil Extracellular Traps Induce Trypsin Activation, Inflammation, and Tissue Damage in Mice with Severe Acute Pancreatitis","volume":"149","author":"Merza","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"20545","DOI":"10.1038\/srep20545","article-title":"Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury","volume":"6","author":"Wu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1083\/jcb.200606027","article-title":"Novel cell death program leads to neutrophil extracellular traps","volume":"176","author":"Fuchs","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/nm.2847","article-title":"Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo","volume":"18","author":"Yipp","year":"2012","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"683445","DOI":"10.3389\/fcvm.2021.683445","article-title":"Diagnostic and Prognostic Value of Neutrophil Extracellular Trap Levels in Patients with Acute Aortic Dissection","volume":"8","author":"Yang","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1084\/jem.20122220","article-title":"Diverse novel functions of neutrophils in immunity, inflammation, and beyond","volume":"210","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1111\/jcmm.12639","article-title":"Central role of neutrophil in the pathogenesis of severe acute pancreatitis","volume":"19","author":"Yang","year":"2015","journal-title":"J. Cell. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fusco, R., Cordaro, M., Siracusa, R., D\u2019Amico, R., Genovese, T., Gugliandolo, E., Peritore, A.F., Crupi, R., Impellizzeri, D., and Cuzzocrea, S. (2020). Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury. Antioxidants, 9.","DOI":"10.3390\/antiox9090781"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/imm.13391","article-title":"Neutrophil-T cell crosstalk in inflammatory bowel disease","volume":"164","author":"Kvedaraite","year":"2021","journal-title":"Immunology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.3389\/fimmu.2018.02171","article-title":"Update on Neutrophil Function in Severe Inflammation","volume":"9","author":"Mortaz","year":"2018","journal-title":"Front Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1136\/gutjnl-2016-313535","article-title":"CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD","volume":"67","author":"Zhou","year":"2018","journal-title":"Gut"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1189\/jlb.0806514","article-title":"Proteinase 3 and CD177 are expressed on the plasma membrane of the same subset of neutrophils","volume":"81","author":"Bauer","year":"2007","journal-title":"J. Leukoc. Biol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/7\/2533\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:04:21Z","timestamp":1760123061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/7\/2533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,27]]},"references-count":35,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["jcm12072533"],"URL":"https:\/\/doi.org\/10.3390\/jcm12072533","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,27]]}}}