Formyl peptide receptor 1 signaling potentiates inflammatory brain injury

作者：Zhiguo Li, Yulin Li, Jinrui Han, Zilong Zhu, Minshu Li, Qiang Liu, Yongjun Wang, Fu‐Dong Shi · 发表于：Science Translational Medicine · 年份：2021 · DOI：10.1126/scitranslmed.abe9890 · 被引用次数：90 · 研究领域：S100 Proteins and Annexins、Immune Response and Inflammation、Neuroinflammation and Neurodegeneration Mechanisms

-formyl peptides, endogenous ligands of FPR1, were augmented and correlated with the magnitude of brain edema in patients with ICH. Interactions of formyl peptides with FPR1 activated microglia, boosted neutrophil recruitment, and aggravated neurological deficits in two mouse models of ICH. We created an FPR1 antagonist T-0080 that can penetrate the brain and bind both human and murine FPR1. T-0080 attenuated brain edema and improved neurological outcomes in ICH models. Thus, FPR1 orchestrates brain inflammation after ICH and could be targeted to improve clinical outcome in patients.