线粒体甲酰肽调节中性粒细胞炎症反应功能的研究进展
Research Progress on the Regulation of Neutrophil Inflammatory Functions by Mitochondrial Formyl Peptides
摘要: 线粒体甲酰肽(mitochondrial Formyl Peptides, mtFPs)是线粒体DNA编码蛋白的裂解产物。细胞受损后，mtFPs作为内源性损伤相关分子模式(Damage-Associated Molecular Patterns, DAMPs)被释放，并被表达甲酰肽受体(Formyl Peptide Receptors, FPRs)的中性粒细胞识别。本文系统综述了mtFPs的释放机制、FPR1和FPR2介导的识别与信号转导，以及mtFPs对中性粒细胞趋化、钙信号、呼吸爆发、吞噬、中性粒细胞胞外诱捕网形成和黏附等功能的调节作用。近年研究发现，mtFPs通过FPRs对中性粒细胞炎症反应发挥双向调节作用——低浓度(10~100 nM) mtFPs可引导中性粒细胞定向迁移至损伤部位并清除坏死组织，而高浓度(>1 μM) mtFPs则导致同源受体脱敏和中性粒细胞功能障碍；同时，mtFPs诱导的中性粒细胞脱敏可增加继发感染风险。靶向FPRs的激动剂与拮抗剂以及清除循环mtFPs的固定化抗体疗法已显示出治疗潜力。进一步阐明mtFPs调控中性粒细胞功能的分子机制，可为无菌性炎症相关疾病的治疗提供新靶点和新策略。
Abstract: Mitochondrial formyl peptides (mtFPs) are cleavage products of proteins encoded by mitochondrial DNA. Upon cell injury, mtFPs are released as endogenous damage-associated molecular patterns (DAMPs) and recognized by neutrophils expressing formyl peptide receptors (FPRs). This review systematically summarizes the release mechanisms of mtFPs, FPR1- and FPR2-mediated recognition and signaling, and the regulatory effects of mtFPs on neutrophil chemotaxis, calcium signaling, respiratory burst, phagocytosis, neutrophil extracellular trap formation, and adhesion. Recent studies have revealed that mtFPs exert bidirectional regulatory effects on neutrophil inflammatory responses via FPRs: low concentrations (10~100 nM) of mtFPs guide neutrophils to injury sites for clearance of necrotic tissues, whereas high concentrations (>1 μM) induce homologous receptor desensitization and neutrophil dysfunction. Meanwhile, mtFP-induced neutrophil desensitization increases the risk of secondary infections. FPR-targeted agonists and antagonists, as well as immobilized antibody-based therapies for clearing circulating mtFPs, have shown therapeutic potential. Further elucidation of the molecular mechanisms underlying mtFP-mediated regulation of neutrophil functions may provide novel therapeutic targets and strategies for sterile inflammatory diseases.
文章引用：杨霞. 线粒体甲酰肽调节中性粒细胞炎症反应功能的研究进展[J]. 临床医学进展, 2026, 16(9): 1916-1924. https://doi.org/10.12677/acm.2026.1693235

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