Cerebral Endothelial CXCR2 Promotes Neutrophil Transmigration into Central Nervous System in LPS-Induced Septic Encephalopathy
Fengjiao Wu,
Yuhong Han,
Qianqian Xiong,
Haitao Tang,
Jing Shi,
Qingqing Yang,
Xuemeng Li,
Haoxuan Jia,
Jun Qian,
Yishu Dong,
Tuantuan Li,
Yong Gao,
Zhongqing Qian,
Hongtao Wang,
Ting Wang
Affiliations
Fengjiao Wu
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China
Yuhong Han
Department of Clinical Laboratory, The Second People’s Hospital of Fuyang City, Fuyang 236015, China
Qianqian Xiong
Department of Clinical Laboratory, Nanjing Meishan Hospital, Nanjing 210041, China
Haitao Tang
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China
Jing Shi
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China
Qingqing Yang
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China
Xuemeng Li
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China
Haoxuan Jia
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China
Jun Qian
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China
Yishu Dong
Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA
Tuantuan Li
Department of Clinical Laboratory, The Second People’s Hospital of Fuyang City, Fuyang 236015, China
Yong Gao
Department of Clinical Laboratory, The Second People’s Hospital of Fuyang City, Fuyang 236015, China
Zhongqing Qian
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China
Hongtao Wang
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China
Ting Wang
Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA
Septic encephalopathy (SE) represents a severe inflammatory syndrome linked to elevated septic mortality rates, lacking specific therapeutic interventions, and often resulting in enduring neurological sequelae. The present investigation endeavors to elucidate the involvement of C-X-C Motif Chemokine Receptor 2 (CXCR2) in the pathogenesis of SE and to explore the potential of CXCR2 modulation as a therapeutic avenue for SE. Employing a murine SE model induced by lipopolysaccharide (LPS) administration, CXCR2 knockout mice and the CXCR2 inhibitor SB225002 were utilized to assess neutrophil recruitment, endothelial integrity, and transendothelial migration. Our findings substantiate that either CXCR2 deficiency or its inhibition curtails neutrophil recruitment without impacting their adhesion to cerebral endothelial cells. This phenomenon is contingent upon endothelial CXCR2 expression rather than CXCR2’s presence on neutrophils. Furthermore, the CXCR2 blockade preserves the integrity of tight junction protein ZO-1 and mitigates F-actin stress fiber formation in cerebral endothelial cells following septic challenge. Mechanistically, CXCL1-mediated CXCR2 activation triggers cerebral endothelial actin contraction via Rho signaling, thereby facilitating neutrophil transmigration in SE. These observations advocate for the potential therapeutic efficacy of CXCR2 inhibition in managing SE.
