Single-cell RNA sequencing reveals S100A8/A9 hi neutrophils-induced endothelial cell death and lymphocyte infiltration after ischemic stroke.

Autor: Wang S; Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China., Wang Y; Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China; State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, 100050, China., Wang S; Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China., Sun Y; Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China., Du Y; Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China., Zhang S; Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China., Yao J; Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China., Wu J; Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China., Xie D; Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: danxiedx@126.com.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 31; Vol. 741, pp. 151023. Date of Electronic Publication: 2024 Nov 19.
DOI: 10.1016/j.bbrc.2024.151023
Abstrakt: Stroke is a major global cause of death and disability, with ischemic stroke being the most common type. The disruption of the blood-brain barrier (BBB) is a key factor in the pathophysiology of ischemic stroke, allowing immune cells to infiltrate and worsening neuroinflammation. This study uses single-cell RNA sequencing (scRNA-seq) to examine the transcriptional changes in neutrophils, endothelial cells, and T cells during ischemic stroke. Our findings indicate a significant increase in neutrophil and lymphocyte infiltration, along with a notable decrease in endothelial cell populations, demonstrating severe BBB disruption. Differential gene expression analysis shows that endothelial cells lose important characteristics post-stroke, while lymphocytes activate cytotoxic pathways that may lead to neuronal damage. Additionally, we reveal the contrasting roles of CXCR2 and CXCR4 in neutrophil movement and identify neutrophil-derived damage-associated molecular patterns (DAMPs) and matrix metalloproteinases (MMPs) as key drivers of endothelial cell apoptosis. Notably, the S100A8/A9 inhibitor paquinimod significantly protects neurons and reduces lymphocyte infiltration, suggesting that targeting S100A8/A9 could be a promising therapeutic strategy for reducing neurological deficits after ischemic stroke. Overall, these results enhance our understanding of the complex interactions between immune cells and the BBB in ischemic stroke, paving the way for innovative therapeutic approaches aimed at maintaining brain integrity and improving patient outcomes.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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