The Pathogenesis of Ischemia-Reperfusion Induced Acute Kidney Injury Depends on Renal Neutrophil Recruitment Whereas Sepsis-Induced AKI Does Not
Acute kidney injury (AKI) may be induced by different causes, including renal ischemia-reperfusion injury and sepsis, which represent the most common reasons for AKI in hospitalized patients. AKI is defined by reduced urine production and/or increased plasma creatinine. However, this definition does...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.843782/full |
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| author | Zhenhan Li Nadine Ludwig Katharina Thomas Sina Mersmann Martin Lehmann Dietmar Vestweber Jean-Francois Pittet Hernando Gomez John A. Kellum Jan Rossaint Alexander Zarbock |
| author_facet | Zhenhan Li Nadine Ludwig Katharina Thomas Sina Mersmann Martin Lehmann Dietmar Vestweber Jean-Francois Pittet Hernando Gomez John A. Kellum Jan Rossaint Alexander Zarbock |
| author_sort | Zhenhan Li |
| collection | DOAJ |
| description | Acute kidney injury (AKI) may be induced by different causes, including renal ischemia-reperfusion injury and sepsis, which represent the most common reasons for AKI in hospitalized patients. AKI is defined by reduced urine production and/or increased plasma creatinine. However, this definition does not address the molecular mechanisms of different AKI entities, and uncertainties remain regarding distinct pathophysiological events causing kidney injury in the first place. In particular, sepsis-induced AKI is considered not to be associated with leukocyte infiltration into the kidney, but a direct investigation of this process is missing to this date. In this study, we used two murine AKI models induced by either renal ischemia-reperfusion injury (IRI) or cecal ligation and puncture (CLP) to investigate the contribution of neutrophils to tissue injury and kidney function. By using VEC-Y731F mice, in which neutrophil recruitment is impaired, we analyzed the specific contribution of neutrophil recruitment to the pathogenesis of IRI- and CLP-induced AKI. We observed that the degree of renal injury evaluated by plasma creatinine, urinary biomarkers and histological analyses, following IRI-induction was dependent on neutrophil migration into the kidney, whereas the pathogenesis of CLP-induced AKI was independent of neutrophil recruitment. Furthermore, plasma transfer experiments suggest that the pathogenesis of CLP-induced AKI relies on circulating inflammatory mediators. These results extend our knowledge of the AKI pathogenesis and may help in the development of prophylactic and therapeutic treatments for AKI patients. |
| first_indexed | 2024-12-10T13:05:09Z |
| format | Article |
| id | doaj.art-643a80cce42f42a292654931518c71c2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T13:05:09Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-643a80cce42f42a292654931518c71c22022-12-22T01:47:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.843782843782The Pathogenesis of Ischemia-Reperfusion Induced Acute Kidney Injury Depends on Renal Neutrophil Recruitment Whereas Sepsis-Induced AKI Does NotZhenhan Li0Nadine Ludwig1Katharina Thomas2Sina Mersmann3Martin Lehmann4Dietmar Vestweber5Jean-Francois Pittet6Hernando Gomez7John A. Kellum8Jan Rossaint9Alexander Zarbock10Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, GermanyDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, GermanyDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, GermanyDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, GermanyDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, GermanyDepartment of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesThe Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesThe Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, GermanyDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, GermanyAcute kidney injury (AKI) may be induced by different causes, including renal ischemia-reperfusion injury and sepsis, which represent the most common reasons for AKI in hospitalized patients. AKI is defined by reduced urine production and/or increased plasma creatinine. However, this definition does not address the molecular mechanisms of different AKI entities, and uncertainties remain regarding distinct pathophysiological events causing kidney injury in the first place. In particular, sepsis-induced AKI is considered not to be associated with leukocyte infiltration into the kidney, but a direct investigation of this process is missing to this date. In this study, we used two murine AKI models induced by either renal ischemia-reperfusion injury (IRI) or cecal ligation and puncture (CLP) to investigate the contribution of neutrophils to tissue injury and kidney function. By using VEC-Y731F mice, in which neutrophil recruitment is impaired, we analyzed the specific contribution of neutrophil recruitment to the pathogenesis of IRI- and CLP-induced AKI. We observed that the degree of renal injury evaluated by plasma creatinine, urinary biomarkers and histological analyses, following IRI-induction was dependent on neutrophil migration into the kidney, whereas the pathogenesis of CLP-induced AKI was independent of neutrophil recruitment. Furthermore, plasma transfer experiments suggest that the pathogenesis of CLP-induced AKI relies on circulating inflammatory mediators. These results extend our knowledge of the AKI pathogenesis and may help in the development of prophylactic and therapeutic treatments for AKI patients.https://www.frontiersin.org/articles/10.3389/fimmu.2022.843782/fullneutrophilskidneyischemia-reperfusion injurycecal ligation and puncturesepsisacute kidney injury |
| spellingShingle | Zhenhan Li Nadine Ludwig Katharina Thomas Sina Mersmann Martin Lehmann Dietmar Vestweber Jean-Francois Pittet Hernando Gomez John A. Kellum Jan Rossaint Alexander Zarbock The Pathogenesis of Ischemia-Reperfusion Induced Acute Kidney Injury Depends on Renal Neutrophil Recruitment Whereas Sepsis-Induced AKI Does Not Frontiers in Immunology neutrophils kidney ischemia-reperfusion injury cecal ligation and puncture sepsis acute kidney injury |
| title | The Pathogenesis of Ischemia-Reperfusion Induced Acute Kidney Injury Depends on Renal Neutrophil Recruitment Whereas Sepsis-Induced AKI Does Not |
| title_full | The Pathogenesis of Ischemia-Reperfusion Induced Acute Kidney Injury Depends on Renal Neutrophil Recruitment Whereas Sepsis-Induced AKI Does Not |
| title_fullStr | The Pathogenesis of Ischemia-Reperfusion Induced Acute Kidney Injury Depends on Renal Neutrophil Recruitment Whereas Sepsis-Induced AKI Does Not |
| title_full_unstemmed | The Pathogenesis of Ischemia-Reperfusion Induced Acute Kidney Injury Depends on Renal Neutrophil Recruitment Whereas Sepsis-Induced AKI Does Not |
| title_short | The Pathogenesis of Ischemia-Reperfusion Induced Acute Kidney Injury Depends on Renal Neutrophil Recruitment Whereas Sepsis-Induced AKI Does Not |
| title_sort | pathogenesis of ischemia reperfusion induced acute kidney injury depends on renal neutrophil recruitment whereas sepsis induced aki does not |
| topic | neutrophils kidney ischemia-reperfusion injury cecal ligation and puncture sepsis acute kidney injury |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.843782/full |
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