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引用次数: 0
摘要
中性粒细胞是哨兵免疫细胞,在抗微生物防御中发挥着重要作用。我们对中性粒细胞组织导航的了解大多来自创伤和感染模型,而过敏性疾病在很大程度上仍被忽视。在这里,我们分析了过敏原挑战的小鼠组织,发现脱颗粒肥大细胞(MC)会将活的中性粒细胞困在其中。肥大细胞释放吸引剂白三烯 B4,将中性粒细胞重新引向肥大细胞,从而利用了中性粒细胞通常用于细胞间通讯的趋化系统。MC 细胞内捕获物(MIT)形成后,中性粒细胞会死亡,但它们未消化的物质会在 MC 空泡中停留数天。MC 可从 MIT 的形成中获益,增强其功能和新陈代谢能力。此外,中性粒细胞还具有更强的促炎作用,并能在一定时间内延迟外渗活性中性粒细胞化合物(内吞作用),从而引起周围巨噬细胞的 1 型干扰素反应。总之,我们的研究强调了中性粒细胞捕获和nexocytosis 是 MC 介导的过程,它们可能在慢性过敏性炎症过程中传递中性粒细胞特征。
Neutrophil trapping and nexocytosis, mast cell-mediated processes for inflammatory signal relay
Neutrophils are sentinel immune cells with essential roles for antimicrobial defense. Most of our knowledge on neutrophil tissue navigation derived from wounding and infection models, whereas allergic conditions remained largely neglected. Here, we analyzed allergen-challenged mouse tissues and discovered that degranulating mast cells (MCs) trap living neutrophils inside them. MCs release the attractant leukotriene B4 to re-route neutrophils toward them, thus exploiting a chemotactic system that neutrophils normally use for intercellular communication. After MC intracellular trap (MIT) formation, neutrophils die, but their undigested material remains inside MC vacuoles over days. MCs benefit from MIT formation, increasing their functional and metabolic fitness. Additionally, they are more pro-inflammatory and can exocytose active neutrophilic compounds with a time delay (nexocytosis), eliciting a type 1 interferon response in surrounding macrophages. Together, our study highlights neutrophil trapping and nexocytosis as MC-mediated processes, which may relay neutrophilic features over the course of chronic allergic inflammation.
期刊介绍:
Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO).
The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries.
In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.