β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury
Abstract Neutrophils are the first responders among peripheral immune cells to infiltrate the central nervous system following a traumatic brain injury (TBI), triggering neuroinflammation that can exacerbate secondary tissue damage. The precise molecular controls that dictate the inflammatory behavi...
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BMC
2025-02-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02071-9 |
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| author | Lei Li Ruilong Peng Cong Wang Xin Chen Dilmurat Gheyret Siyu Guan Bo Chen Yafan Liu Xilei Liu Yiyao Cao Cha Han Jianhua Xiong Fanjian Li Taoyuan Lu Haoran Jia Kaiji Li Jinchao Wang Xu Zhang Jianye Xu Yajuan Wang Xin Xu Tuo Li Jianning Zhang Shu Zhang |
| author_facet | Lei Li Ruilong Peng Cong Wang Xin Chen Dilmurat Gheyret Siyu Guan Bo Chen Yafan Liu Xilei Liu Yiyao Cao Cha Han Jianhua Xiong Fanjian Li Taoyuan Lu Haoran Jia Kaiji Li Jinchao Wang Xu Zhang Jianye Xu Yajuan Wang Xin Xu Tuo Li Jianning Zhang Shu Zhang |
| author_sort | Lei Li |
| collection | DOAJ |
| description | Abstract Neutrophils are the first responders among peripheral immune cells to infiltrate the central nervous system following a traumatic brain injury (TBI), triggering neuroinflammation that can exacerbate secondary tissue damage. The precise molecular controls that dictate the inflammatory behavior of neutrophils post-TBI, however, remain largely elusive. Our comprehensive analysis of the molecular landscape surrounding the trauma in TBI mice has revealed a significant alteration in the abundance of β2 integrin (ITGB2), predominantly expressed by neutrophils and closely associated with immune responses. Using the fluid percussion injury (FPI) mouse model, we investigated the therapeutic efficacy of Rovelizumab, an agent that blocks ITGB2. The treatment has demonstrated significant improvements in neurologic function in TBI mice, attenuating blood–brain barrier permeability, mitigating oxidative stress and inflammatory mediator release, and enhancing cerebral perfusion. Moreover, ITGB2 blockade has effectively limited the adherence, migration, and infiltration of neutrophils, and has impeded the formation of neutrophil extracellular traps (NETs) upon their activation. Finally, it was demonstrated that ITGB2 mediates these effects mainly through its interaction with intercellular adhesion molecule-1 (ICAM 1) of endotheliocyte. These findings collectively illuminate ITGB2 as a crucial molecular switch that governs the adverse effects of neutrophils post-TBI and could be targeted to improve clinical outcome in patients. |
| format | Article |
| id | doaj-art-0e98d584b67e470a96a4dc0b4206ee20 |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-0e98d584b67e470a96a4dc0b4206ee202025-02-09T12:47:22ZengBMCCell Communication and Signaling1478-811X2025-02-0123112110.1186/s12964-025-02071-9β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injuryLei Li0Ruilong Peng1Cong Wang2Xin Chen3Dilmurat Gheyret4Siyu Guan5Bo Chen6Yafan Liu7Xilei Liu8Yiyao Cao9Cha Han10Jianhua Xiong11Fanjian Li12Taoyuan Lu13Haoran Jia14Kaiji Li15Jinchao Wang16Xu Zhang17Jianye Xu18Yajuan Wang19Xin Xu20Tuo Li21Jianning Zhang22Shu Zhang23Department of Neurosurgery, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Huanhu HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalKey Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute, Ministry of EducationDepartment of Neurosurgery, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalDepartment of Urology, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalDepartment of Gynecology and Obstetrics, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalXuanwu Jinan HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalKey Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute, Ministry of EducationDepartment of Neurosurgery, Tianjin Medical University General HospitalKey Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute, Ministry of EducationXuanwu Jinan HospitalDepartment of Neurosurgery, Tianjin Huanhu HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalDepartment of Neurosurgery, Tianjin Medical University General HospitalAbstract Neutrophils are the first responders among peripheral immune cells to infiltrate the central nervous system following a traumatic brain injury (TBI), triggering neuroinflammation that can exacerbate secondary tissue damage. The precise molecular controls that dictate the inflammatory behavior of neutrophils post-TBI, however, remain largely elusive. Our comprehensive analysis of the molecular landscape surrounding the trauma in TBI mice has revealed a significant alteration in the abundance of β2 integrin (ITGB2), predominantly expressed by neutrophils and closely associated with immune responses. Using the fluid percussion injury (FPI) mouse model, we investigated the therapeutic efficacy of Rovelizumab, an agent that blocks ITGB2. The treatment has demonstrated significant improvements in neurologic function in TBI mice, attenuating blood–brain barrier permeability, mitigating oxidative stress and inflammatory mediator release, and enhancing cerebral perfusion. Moreover, ITGB2 blockade has effectively limited the adherence, migration, and infiltration of neutrophils, and has impeded the formation of neutrophil extracellular traps (NETs) upon their activation. Finally, it was demonstrated that ITGB2 mediates these effects mainly through its interaction with intercellular adhesion molecule-1 (ICAM 1) of endotheliocyte. These findings collectively illuminate ITGB2 as a crucial molecular switch that governs the adverse effects of neutrophils post-TBI and could be targeted to improve clinical outcome in patients.https://doi.org/10.1186/s12964-025-02071-9Traumatic brain injuryNeuroinflammationβ2 integrinNeutrophil extracellular trapsIntercellular adhesion molecule-1 |
| spellingShingle | Lei Li Ruilong Peng Cong Wang Xin Chen Dilmurat Gheyret Siyu Guan Bo Chen Yafan Liu Xilei Liu Yiyao Cao Cha Han Jianhua Xiong Fanjian Li Taoyuan Lu Haoran Jia Kaiji Li Jinchao Wang Xu Zhang Jianye Xu Yajuan Wang Xin Xu Tuo Li Jianning Zhang Shu Zhang β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury Cell Communication and Signaling Traumatic brain injury Neuroinflammation β2 integrin Neutrophil extracellular traps Intercellular adhesion molecule-1 |
| title | β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury |
| title_full | β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury |
| title_fullStr | β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury |
| title_full_unstemmed | β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury |
| title_short | β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury |
| title_sort | β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury |
| topic | Traumatic brain injury Neuroinflammation β2 integrin Neutrophil extracellular traps Intercellular adhesion molecule-1 |
| url | https://doi.org/10.1186/s12964-025-02071-9 |
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