2. Academic Validation
  3. β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury

β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury

  • Cell Commun Signal. 2025 Feb 8;23(1):70. doi: 10.1186/s12964-025-02071-9.
Lei Li # 1 2,  Ruilong Peng # 3,  Cong Wang # 1 2,  Xin Chen # 1 2,  Dilmurat Gheyret 1 2,  Siyu Guan 2,  Bo Chen 1 2,  Yafan Liu 1 2,  Xilei Liu 4,  Yiyao Cao 1,  Cha Han 5 6,  Jianhua Xiong 1 2,  Fanjian Li 1 2,  Taoyuan Lu 7 8,  Haoran Jia 1 2,  Kaiji Li 1 2,  Jinchao Wang 1 2,  Xu Zhang 2 9,  Jianye Xu 1 2,  Yajuan Wang 2 5,  Xin Xu 10 11,  Tuo Li 12,  Jianning Zhang 13 14,  Shu Zhang 15 16
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
  • 2 Key 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 Education, Tianjin, 300052, China.
  • 3 Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, 300200, China.
  • 4 Department of Urology, Tianjin Medical University General Hospital, Tianjin, 300052, China.
  • 5 Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, China.
  • 6 Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, 300052, China.
  • 7 Xuanwu Jinan Hospital, 5106 Jingshi Road, Jinan, 250000, Shandong, China.
  • 8 Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.
  • 9 School of Medicine, Nankai University, Tianjin, 300071, China.
  • 10 Xuanwu Jinan Hospital, 5106 Jingshi Road, Jinan, 250000, Shandong, China. xuxindoc@hotmail.com.
  • 11 Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China. xuxindoc@hotmail.com.
  • 12 Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, 300200, China. ytdzlt3528@tmu.edu.cn.
  • 13 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China. jianningzhang@hotmail.com.
  • 14 Key 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 Education, Tianjin, 300052, China. jianningzhang@hotmail.com.
  • 15 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China. gloria523@163.com.
  • 16 Key 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 Education, Tianjin, 300052, China. gloria523@163.com.
  • # Contributed equally.
PMID: 39923080 DOI: 10.1186/s12964-025-02071-9
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.

Keywords

Intercellular adhesion molecule-1; Neuroinflammation; Neutrophil extracellular traps; Traumatic brain injury; β2 integrin.

Figures
Products