Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS
IntroductionThe severity of spinal cord injury (SCI) is closely tied to pulmonary function, especially in cases of higher SCI levels. Despite this connection, the underlying pathological mechanisms in the lungs post-SCI are not well understood. Previous research has established a connection between...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483402/full |
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| author | Bradford C. Berk Bradford C. Berk Amanda Pereira Velia Sofia Vizcarra Christoph Pröschel Chia George Hsu Chia George Hsu Chia George Hsu |
| author_facet | Bradford C. Berk Bradford C. Berk Amanda Pereira Velia Sofia Vizcarra Christoph Pröschel Chia George Hsu Chia George Hsu Chia George Hsu |
| author_sort | Bradford C. Berk |
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| description | IntroductionThe severity of spinal cord injury (SCI) is closely tied to pulmonary function, especially in cases of higher SCI levels. Despite this connection, the underlying pathological mechanisms in the lungs post-SCI are not well understood. Previous research has established a connection between disrupted sympathetic regulation and splenocyte apoptosis in high thoracic SCI, leading to pulmonary dysfunction. The aim of this study was to investigate whether mice with low-level SCI exhibit increased susceptibility to acute lung injury by eliciting systemic inflammatory responses that operate independently of the sympathetic nervous system. MethodsHere, we employed T9 contusion SCI and exposed mice to aerosolized lipopolysaccharide (LPS) to simulate lung inflammation associated with acute respiratory distress syndrome (ARDS). Twenty-four hours post-LPS exposure, lung tissues and bronchoalveolar lavage (BAL) fluid were analyzed. ResultsLPS markedly induced proinflammatory gene expression (SAA3, IRG1, NLRP3, IL-1beta, MCP-1) and cytokine release (IL-1beta, IL-6, MCP-1) in SCI mice compared to controls, indicating an exaggerated inflammatory response. Infiltration of Ly6G/C positive neutrophils and macrophages was significantly higher in SCI mice lungs post-LPS exposure. Interestingly, spleen size and weight did not differ between control and SCI mice, suggesting that T9 SCI alone does not cause spleen atrophy. Notably, bone-marrow-derived macrophages (BMDMs) from SCI mice exhibited hyper-responsiveness to LPS. DiscussionsThis study demonstrated an increase in lung inflammation and immune responses subsequent to low-level T9 SCI, underscoring the widespread influence of systemic inflammation post-SCI, especially pronounced in specific organs like the lungs. |
| format | Article |
| id | doaj-art-19757749972144459bb7d348e4d4534e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-19757749972144459bb7d348e4d4534e2025-01-15T05:10:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14834021483402Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPSBradford C. Berk0Bradford C. Berk1Amanda Pereira2Velia Sofia Vizcarra3Christoph Pröschel4Chia George Hsu5Chia George Hsu6Chia George Hsu7Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesDepartment of Physical Medicine and Rehabilitation, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesDepartment of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesDepartment of Translational Biomedical Science, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesDepartment of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesDepartment of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesDepartment of Kinesiology, University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Molecular Microbiology and Immunology, University of Texas at San Antonio, San Antonio, TX, United StatesIntroductionThe severity of spinal cord injury (SCI) is closely tied to pulmonary function, especially in cases of higher SCI levels. Despite this connection, the underlying pathological mechanisms in the lungs post-SCI are not well understood. Previous research has established a connection between disrupted sympathetic regulation and splenocyte apoptosis in high thoracic SCI, leading to pulmonary dysfunction. The aim of this study was to investigate whether mice with low-level SCI exhibit increased susceptibility to acute lung injury by eliciting systemic inflammatory responses that operate independently of the sympathetic nervous system. MethodsHere, we employed T9 contusion SCI and exposed mice to aerosolized lipopolysaccharide (LPS) to simulate lung inflammation associated with acute respiratory distress syndrome (ARDS). Twenty-four hours post-LPS exposure, lung tissues and bronchoalveolar lavage (BAL) fluid were analyzed. ResultsLPS markedly induced proinflammatory gene expression (SAA3, IRG1, NLRP3, IL-1beta, MCP-1) and cytokine release (IL-1beta, IL-6, MCP-1) in SCI mice compared to controls, indicating an exaggerated inflammatory response. Infiltration of Ly6G/C positive neutrophils and macrophages was significantly higher in SCI mice lungs post-LPS exposure. Interestingly, spleen size and weight did not differ between control and SCI mice, suggesting that T9 SCI alone does not cause spleen atrophy. Notably, bone-marrow-derived macrophages (BMDMs) from SCI mice exhibited hyper-responsiveness to LPS. DiscussionsThis study demonstrated an increase in lung inflammation and immune responses subsequent to low-level T9 SCI, underscoring the widespread influence of systemic inflammation post-SCI, especially pronounced in specific organs like the lungs. https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483402/fullspinal cord injuryinflammationacute lung injurymacrophagepulmonary dysfunction |
| spellingShingle | Bradford C. Berk Bradford C. Berk Amanda Pereira Velia Sofia Vizcarra Christoph Pröschel Chia George Hsu Chia George Hsu Chia George Hsu Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS Frontiers in Immunology spinal cord injury inflammation acute lung injury macrophage pulmonary dysfunction |
| title | Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS |
| title_full | Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS |
| title_fullStr | Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS |
| title_full_unstemmed | Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS |
| title_short | Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS |
| title_sort | spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to lps |
| topic | spinal cord injury inflammation acute lung injury macrophage pulmonary dysfunction |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483402/full |
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