Shao Yiming, Zheng Qibing, Zhang Xiaobei, Li Ping, Gao Xingxin, Zhang Liming, Xu Jiahong, Meng Lingchao, Tian Yanyun, Zhang Qinqin, Zhou Guangxi
Taishan Scholars Laboratory, Affiliated Hospital of Jining Medical University, Jining 272000, China.
Department of Burns and Plastic Surgery, Affiliated Hospital of Jining Medical University, Jining 272000, China.
Precis Clin Med. 2024 Oct 14;7(4):pbae028. doi: 10.1093/pcmedi/pbae028. eCollection 2024 Dec.
Both intestinal and pulmonary systems are parts of the mucosal immune system, comprising ∼80% of all immune cells. These immune cells migrate or are transported between various mucosal tissues to maintain tissue homeostasis.
In this study, we isolated neutrophils from the peripheral blood of patients and utilized immunofluorescence, flow cytometry, and Western blotting to confirm the incidence of "nucleus-directed degranulation" . Subsequently, we conducted a precise analysis using arivis software. Furthermore, using the DSS mouse model of colitis and tissue clearing technologies, we validated the "targeted nuclear degranulation" of neutrophils and their migration to the lungs in an inflammatory intestinal environment.
In this study, we found that among patients with ulcerative colitis, the migration of neutrophils with "targeted nuclear degranulation" from the intestinal mucosa to the lungs significantly exacerbates lung inflammation during pulmonary infections. Notably, patients with ulcerative colitis exhibited a higher abundance of neutrophils with targeted nuclear degranulation. Using DSS mice, we observed that neutrophils with targeted nuclear degranulation from the intestinal mucosa migrated to the lung and underwent activation during pulmonary infections. These neutrophils rapidly released a high amount of neutrophil extracellular traps to mediate the progression of lung inflammation. Alterations in the neutrophil cytoskeleton and its interaction with the nuclear membrane represent the primary mechanisms underlying targeted nuclear degranulation.
This study revealed that neutrophils accelerate lung inflammation progression in colitis, offering new insights and potential treatment targets for lung infections for patients with colitis.
肠道和肺部系统均为黏膜免疫系统的组成部分，约占所有免疫细胞的80%。这些免疫细胞在各种黏膜组织之间迁移或转运，以维持组织稳态。
在本研究中，我们从患者外周血中分离出中性粒细胞，并利用免疫荧光、流式细胞术和蛋白质免疫印迹法来确认“细胞核定向脱颗粒”的发生率。随后，我们使用阿瑞维斯软件进行了精确分析。此外，利用结肠炎的葡聚糖硫酸钠（DSS）小鼠模型和组织透明化技术，我们验证了中性粒细胞在炎症性肠道环境中的“靶向细胞核脱颗粒”及其向肺部的迁移。
在本研究中，我们发现，在溃疡性结肠炎患者中，具有“靶向细胞核脱颗粒”的中性粒细胞从肠道黏膜向肺部的迁移在肺部感染期间会显著加剧肺部炎症。值得注意的是，溃疡性结肠炎患者中具有靶向细胞核脱颗粒的中性粒细胞丰度更高。使用DSS小鼠，我们观察到来自肠道黏膜的具有靶向细胞核脱颗粒的中性粒细胞在肺部感染期间迁移至肺部并被激活。这些中性粒细胞迅速释放大量中性粒细胞胞外陷阱，以介导肺部炎症的进展。中性粒细胞细胞骨架的改变及其与核膜的相互作用是靶向细胞核脱颗粒的主要机制。
本研究表明，中性粒细胞会加速结肠炎患者肺部炎症的进展，为结肠炎患者肺部感染提供了新的见解和潜在治疗靶点。
