Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents
<b>Background</b>: Neutrophils are thought to play a pivotal role in the pathogenesis of many inflammatory diseases, such as hepatitis, liver cirrhosis, etc. Activated human neutrophils release human neutrophil peptides (HNP1-3) or alpha-defensins that are antimicrobial peptides in azuro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/13/5/1237 |
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| author | Anna Rycyk-Bojarzyńska Beata Kasztelan-Szczerbińska Halina Cichoż-Lach Agata Surdacka Jacek Roliński |
| author_facet | Anna Rycyk-Bojarzyńska Beata Kasztelan-Szczerbińska Halina Cichoż-Lach Agata Surdacka Jacek Roliński |
| author_sort | Anna Rycyk-Bojarzyńska |
| collection | DOAJ |
| description | <b>Background</b>: Neutrophils are thought to play a pivotal role in the pathogenesis of many inflammatory diseases, such as hepatitis, liver cirrhosis, etc. Activated human neutrophils release human neutrophil peptides (HNP1-3) or alpha-defensins that are antimicrobial peptides in azurophil granules. Furthermore, HNP1-3 build a scaffold of neutrophil extracellular traps (NETs) and promote the process of programmed cell death called NETosis. Our study aimed to investigate the role of alpha-defensins in the pathogenesis of alcohol-related liver cirrhosis (ALC). <b>Methods:</b> The concentrations of alpha-defensins in the plasma of 62 patients with ALC and 24 healthy subjects were measured by ELISA. The patients with ALC were prospectively recruited based on the severity of liver dysfunction according to the Child-Pugh and Model of End-Stage Liver Disease-Natrium (MELD-Na) scores, modified Maddrey’s Discriminant Function (mDF), and the presence of ALC complications. <b>Results:</b> The concentrations of alpha-defensins in plasma were significantly higher in the ALC patients than in the controls. The plasma levels of HNP1-3 correlated with the MELD and mDF scores. ALC subgroups with MELD > 20 and mDF > 32 displayed significantly higher HNP1-3 concentrations. The plasma levels of HNP1-3 revealed a good predictive AUC for hepatic encephalopathy and ascites development (0.81 and 0.74, respectively) and for patient survival (0.87) in those over 40 years of age. <b>Conclusion:</b> These findings suggest that alpha-defensins play an important role in the assessment of ALC. |
| first_indexed | 2024-04-25T00:26:30Z |
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| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-04-25T00:26:30Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-4a7a2c42fbd3414d941355c099322a302024-03-12T16:47:39ZengMDPI AGJournal of Clinical Medicine2077-03832024-02-01135123710.3390/jcm13051237Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic AgentsAnna Rycyk-Bojarzyńska0Beata Kasztelan-Szczerbińska1Halina Cichoż-Lach2Agata Surdacka3Jacek Roliński4Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 20-059 Lublin, PolandDepartment of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 20-059 Lublin, PolandDepartment of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 20-059 Lublin, PolandDepartment of Clinical Immunology, Medical University of Lublin, 20-059 Lublin, PolandDepartment of Clinical Immunology, Medical University of Lublin, 20-059 Lublin, Poland<b>Background</b>: Neutrophils are thought to play a pivotal role in the pathogenesis of many inflammatory diseases, such as hepatitis, liver cirrhosis, etc. Activated human neutrophils release human neutrophil peptides (HNP1-3) or alpha-defensins that are antimicrobial peptides in azurophil granules. Furthermore, HNP1-3 build a scaffold of neutrophil extracellular traps (NETs) and promote the process of programmed cell death called NETosis. Our study aimed to investigate the role of alpha-defensins in the pathogenesis of alcohol-related liver cirrhosis (ALC). <b>Methods:</b> The concentrations of alpha-defensins in the plasma of 62 patients with ALC and 24 healthy subjects were measured by ELISA. The patients with ALC were prospectively recruited based on the severity of liver dysfunction according to the Child-Pugh and Model of End-Stage Liver Disease-Natrium (MELD-Na) scores, modified Maddrey’s Discriminant Function (mDF), and the presence of ALC complications. <b>Results:</b> The concentrations of alpha-defensins in plasma were significantly higher in the ALC patients than in the controls. The plasma levels of HNP1-3 correlated with the MELD and mDF scores. ALC subgroups with MELD > 20 and mDF > 32 displayed significantly higher HNP1-3 concentrations. The plasma levels of HNP1-3 revealed a good predictive AUC for hepatic encephalopathy and ascites development (0.81 and 0.74, respectively) and for patient survival (0.87) in those over 40 years of age. <b>Conclusion:</b> These findings suggest that alpha-defensins play an important role in the assessment of ALC.https://www.mdpi.com/2077-0383/13/5/1237alpha-defensinshuman neutrophil peptides (HNPs)neutrophilsNETosisneutrophil extracellular trap (NET)alcohol-related liver cirrhosis |
| spellingShingle | Anna Rycyk-Bojarzyńska Beata Kasztelan-Szczerbińska Halina Cichoż-Lach Agata Surdacka Jacek Roliński Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents Journal of Clinical Medicine alpha-defensins human neutrophil peptides (HNPs) neutrophils NETosis neutrophil extracellular trap (NET) alcohol-related liver cirrhosis |
| title | Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents |
| title_full | Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents |
| title_fullStr | Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents |
| title_full_unstemmed | Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents |
| title_short | Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents |
| title_sort | human neutrophil alpha defensins promote netosis and liver injury in alcohol related liver cirrhosis potential therapeutic agents |
| topic | alpha-defensins human neutrophil peptides (HNPs) neutrophils NETosis neutrophil extracellular trap (NET) alcohol-related liver cirrhosis |
| url | https://www.mdpi.com/2077-0383/13/5/1237 |
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