Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple Injury
The immune response following trauma represents a major driving force of organ dysfunction and poor outcome. Therefore, we investigated the influence of an additional hemorrhagic shock (HS) on the early posttraumatic immune dysbalance in the whole population of blood leukocytes. A well-established m...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/6654318 |
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| author | Lisa Debler Annette Palmer Sonja Braumüller Bettina Klohs Tom Eirik Mollnes Karlheinz Holzmann Markus Huber-Lang Rebecca Halbgebauer |
| author_facet | Lisa Debler Annette Palmer Sonja Braumüller Bettina Klohs Tom Eirik Mollnes Karlheinz Holzmann Markus Huber-Lang Rebecca Halbgebauer |
| author_sort | Lisa Debler |
| collection | DOAJ |
| description | The immune response following trauma represents a major driving force of organ dysfunction and poor outcome. Therefore, we investigated the influence of an additional hemorrhagic shock (HS) on the early posttraumatic immune dysbalance in the whole population of blood leukocytes. A well-established murine polytrauma (PT) model with or without an additional pressure-controlled HS (mean arterial pressure of 30 mmHg (±5 mmHg) for 60 mins, afterwards fluid resuscitation with balanced electrolyte solution four times the volume of blood drawn) was used. C57BL/6 mice were randomized into a control, PT, and PT + HS group with three animals in each group. Four hours after trauma, corresponding to three hours after induction of hemorrhage, RNA was isolated from all peripheral blood leukocytes, and a microarray analysis was performed. Enrichment analysis was conducted on selected genes strongly modulated by the HS. After additional HS in PT mice, the gene expression of pathways related to the innate immunity, such as IL-6 production, neutrophil chemotaxis, cell adhesion, and toll-like receptor signaling was upregulated, whereas pathways of the adaptive immune system, such as B- and T-cell activation as well as the MHC class II protein complex, were downregulated. These results demonstrate that an additional HS plays an important role in the immune dysregulation early after PT by shifting the balance to increased innate and reduced adaptive immune responses. |
| format | Article |
| id | doaj-art-76d38d44d7d2439db8adcd708ca57511 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-76d38d44d7d2439db8adcd708ca575112025-02-03T05:49:17ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/66543186654318Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple InjuryLisa Debler0Annette Palmer1Sonja Braumüller2Bettina Klohs3Tom Eirik Mollnes4Karlheinz Holzmann5Markus Huber-Lang6Rebecca Halbgebauer7Institute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Ulm, GermanyInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Ulm, GermanyInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Ulm, GermanyInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Ulm, GermanyDepartment of Immunology, Oslo University Hospital, and University of Oslo, NorwayCore Facility Genomics, Ulm University, Ulm, GermanyInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Ulm, GermanyInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Ulm, GermanyThe immune response following trauma represents a major driving force of organ dysfunction and poor outcome. Therefore, we investigated the influence of an additional hemorrhagic shock (HS) on the early posttraumatic immune dysbalance in the whole population of blood leukocytes. A well-established murine polytrauma (PT) model with or without an additional pressure-controlled HS (mean arterial pressure of 30 mmHg (±5 mmHg) for 60 mins, afterwards fluid resuscitation with balanced electrolyte solution four times the volume of blood drawn) was used. C57BL/6 mice were randomized into a control, PT, and PT + HS group with three animals in each group. Four hours after trauma, corresponding to three hours after induction of hemorrhage, RNA was isolated from all peripheral blood leukocytes, and a microarray analysis was performed. Enrichment analysis was conducted on selected genes strongly modulated by the HS. After additional HS in PT mice, the gene expression of pathways related to the innate immunity, such as IL-6 production, neutrophil chemotaxis, cell adhesion, and toll-like receptor signaling was upregulated, whereas pathways of the adaptive immune system, such as B- and T-cell activation as well as the MHC class II protein complex, were downregulated. These results demonstrate that an additional HS plays an important role in the immune dysregulation early after PT by shifting the balance to increased innate and reduced adaptive immune responses.http://dx.doi.org/10.1155/2021/6654318 |
| spellingShingle | Lisa Debler Annette Palmer Sonja Braumüller Bettina Klohs Tom Eirik Mollnes Karlheinz Holzmann Markus Huber-Lang Rebecca Halbgebauer Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple Injury Mediators of Inflammation |
| title | Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple Injury |
| title_full | Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple Injury |
| title_fullStr | Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple Injury |
| title_full_unstemmed | Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple Injury |
| title_short | Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple Injury |
| title_sort | hemorrhagic shock induces a rapid transcriptomic shift of the immune balance in leukocytes after experimental multiple injury |
| url | http://dx.doi.org/10.1155/2021/6654318 |
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