Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis model
Abstract Background Neutrophil granulocytes are important parts of the defence against bacterial infections. Their action is a two-edged sword, the mediators killing the intruding bacteria are at the same time causing tissue damage. Neutrophil activation is part of the dysregulated immune response t...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2025-02-01
|
| Series: | Intensive Care Medicine Experimental |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40635-025-00721-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823863572191510528 |
|---|---|
| author | Frida Wilske Olof Eriksson Rose-Marie Amini Sergio Estrada Helena Janols Amina Khalil Anders Larsson Miklós Lipcsey Sara Mangsbo Jonathan Sigfridsson Jan Sjölin Paul Skorup Anders Wall Viola Wilson Markus Castegren Gunnar Antoni |
| author_facet | Frida Wilske Olof Eriksson Rose-Marie Amini Sergio Estrada Helena Janols Amina Khalil Anders Larsson Miklós Lipcsey Sara Mangsbo Jonathan Sigfridsson Jan Sjölin Paul Skorup Anders Wall Viola Wilson Markus Castegren Gunnar Antoni |
| author_sort | Frida Wilske |
| collection | DOAJ |
| description | Abstract Background Neutrophil granulocytes are important parts of the defence against bacterial infections. Their action is a two-edged sword, the mediators killing the intruding bacteria are at the same time causing tissue damage. Neutrophil activation is part of the dysregulated immune response to infection defining sepsis and neutrophil elastase is one of the powerful proteases causing both effects and damage. Inhibition of neutrophil elastase has been tried in sepsis and ARDS, so far with inconclusive results. Methods We used positron emission tomography (PET) combined with computed tomography (CT) and the selective and specific neutrophil elastase inhibitor PET-tracer [11C]GW457427 ([11C]NES), in an intensive care unit porcine Escherichia coli sepsis model with the primary aim to visualise the biodistribution of neutrophil elastase in the initial acute phase of the septic reaction. Repeated PET–CT investigations were performed before and after induction of sepsis. Results At baseline [11C]NES uptake was found in the bone marrow, spleen and liver. The uptake in the bone marrow was markedly increased two hours into the sepsis, whereas in spleen and liver the uptake was not as markedly changed compared to baseline. At 4 h after the sepsis induction [11C]NES in the bone marrow decreased while the uptake increased in the spleen, liver and lungs. Conclusion The neutrophil elastase PET-tracer [11C]NES is a novel and unique instrument to study the acute innate neutrophil immune response in sepsis and associated vital organ failure. We here present images and quantitative data of the neutrophil elastase distribution the first hours of acute experimental sepsis. Surprisingly, a pronounced increase of neutrophil elastase was found in the bone marrow 2 h into the sepsis reaction followed at 4 h by increase in the liver, spleen and lungs and a concomitant reduction of the tracer uptake in bone marrow. |
| format | Article |
| id | doaj-art-0187df48856a40b18963cbe589804610 |
| institution | Kabale University |
| issn | 2197-425X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Intensive Care Medicine Experimental |
| spelling | doaj-art-0187df48856a40b18963cbe5898046102025-02-09T12:04:35ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2025-02-0113111310.1186/s40635-025-00721-3Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis modelFrida Wilske0Olof Eriksson1Rose-Marie Amini2Sergio Estrada3Helena Janols4Amina Khalil5Anders Larsson6Miklós Lipcsey7Sara Mangsbo8Jonathan Sigfridsson9Jan Sjölin10Paul Skorup11Anders Wall12Viola Wilson13Markus Castegren14Gunnar Antoni15Department of Medical Sciences, Infectious Diseases, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityDepartment of Medicinal Chemistry, Uppsala UniversityDepartment of Medical Sciences, Infectious Diseases, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityDepartment of Medical Sciences, Clinical Chemistry, Uppsala UniversityDepartment of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala UniversityDepartment of Pharmacy, Uppsala UniversityDepartment of Surgical Sciences, Molecular Imaging and Medical Physics, Uppsala UniversityDepartment of Medical Sciences, Infectious Diseases, Uppsala UniversityDepartment of Medical Sciences, Infectious Diseases, Uppsala UniversityDepartment of Surgical Sciences, Molecular Imaging and Medical Physics, Uppsala UniversityDepartment of Medicinal Chemistry, Uppsala UniversityDepartment of Medical Sciences, Infectious Diseases, Uppsala UniversityDepartment of Medicinal Chemistry, Uppsala UniversityAbstract Background Neutrophil granulocytes are important parts of the defence against bacterial infections. Their action is a two-edged sword, the mediators killing the intruding bacteria are at the same time causing tissue damage. Neutrophil activation is part of the dysregulated immune response to infection defining sepsis and neutrophil elastase is one of the powerful proteases causing both effects and damage. Inhibition of neutrophil elastase has been tried in sepsis and ARDS, so far with inconclusive results. Methods We used positron emission tomography (PET) combined with computed tomography (CT) and the selective and specific neutrophil elastase inhibitor PET-tracer [11C]GW457427 ([11C]NES), in an intensive care unit porcine Escherichia coli sepsis model with the primary aim to visualise the biodistribution of neutrophil elastase in the initial acute phase of the septic reaction. Repeated PET–CT investigations were performed before and after induction of sepsis. Results At baseline [11C]NES uptake was found in the bone marrow, spleen and liver. The uptake in the bone marrow was markedly increased two hours into the sepsis, whereas in spleen and liver the uptake was not as markedly changed compared to baseline. At 4 h after the sepsis induction [11C]NES in the bone marrow decreased while the uptake increased in the spleen, liver and lungs. Conclusion The neutrophil elastase PET-tracer [11C]NES is a novel and unique instrument to study the acute innate neutrophil immune response in sepsis and associated vital organ failure. We here present images and quantitative data of the neutrophil elastase distribution the first hours of acute experimental sepsis. Surprisingly, a pronounced increase of neutrophil elastase was found in the bone marrow 2 h into the sepsis reaction followed at 4 h by increase in the liver, spleen and lungs and a concomitant reduction of the tracer uptake in bone marrow.https://doi.org/10.1186/s40635-025-00721-3PorcineSepsisPETNeutrophil elastaseE coli[11C]NES |
| spellingShingle | Frida Wilske Olof Eriksson Rose-Marie Amini Sergio Estrada Helena Janols Amina Khalil Anders Larsson Miklós Lipcsey Sara Mangsbo Jonathan Sigfridsson Jan Sjölin Paul Skorup Anders Wall Viola Wilson Markus Castegren Gunnar Antoni Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis model Intensive Care Medicine Experimental Porcine Sepsis PET Neutrophil elastase E coli [11C]NES |
| title | Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis model |
| title_full | Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis model |
| title_fullStr | Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis model |
| title_full_unstemmed | Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis model |
| title_short | Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis model |
| title_sort | repeated positron emission tomography tracing neutrophil elastase in a porcine intensive care sepsis model |
| topic | Porcine Sepsis PET Neutrophil elastase E coli [11C]NES |
| url | https://doi.org/10.1186/s40635-025-00721-3 |
| work_keys_str_mv | AT fridawilske repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT oloferiksson repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT rosemarieamini repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT sergioestrada repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT helenajanols repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT aminakhalil repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT anderslarsson repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT mikloslipcsey repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT saramangsbo repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT jonathansigfridsson repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT jansjolin repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT paulskorup repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT anderswall repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT violawilson repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT markuscastegren repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel AT gunnarantoni repeatedpositronemissiontomographytracingneutrophilelastaseinaporcineintensivecaresepsismodel |