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细胞内和度的同时增加可以促进巨细胞的抗菌活性
Luka Krampert1, Thomas Ossner1, Agnes Schröder1,2
1Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg and University of Regensburg, 93053 Regensburg, Germany.
Cells
|December 22, 2023
概括
高盐环境通过增加细胞内来促进巨细胞的抗菌功能. 然而,仅仅增加细胞内的心脏糖化物并不能完全复制这种效应,这表明高血压压力也至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生理学 细胞生理学
- 生物化学 生物化学
背景情况:
- 炎症和感染增加局部 (Na+) 水平,影响免疫细胞功能.
- 高盐 (HS) 条件通过Na+/Ca2+交换器1 (NCX1) 在巨细胞中提升细胞内Na+,增强了护信号传递和促炎反应.
- 这包括增加2型氧化合成酶表达和改善的抗菌活性.
研究的目的:
- 调查高细胞内Na+在巨细胞功能中的特定作用.
- 在调节巨细胞反应时,区分细胞内Na+积累与高压的作用.
主要方法:
- 药理上抑制Na+/K+-ATPase (NKA) 使用心脏糖化物 (ouabain和消毒素) 来增加细胞内Na+而不会改变细胞外Na+.
- 巨细胞暴露在高盐 (HS) 条件下.
- 对细胞内离子度 (Na+,Ca2+,K+),p38/MAPK酸化,激活T细胞5 (NFAT5) 表达的核因子,氧化 (NO) 生产和细菌消除的分析.
- 与ouabain和mannitol (MAN) 同时治疗,以评估高血压压力的作用.
主要成果:
- 这两种HS条件和NKA抑制 (ouabain,digoxin) 都导致了细胞内Na+积累和p38/MAPK酸化.
- 与HS相比,心脏糖化物诱导了不同的细胞内Ca2+和K+动态.
- NFAT5并没有被ouabain或digoxin上调调节,并且氧化的产生也没有得到增强.
- 抗微生物活性被心脏糖化物异质地影响,与曼尼托尔的联合治疗部分模仿了HS增强的活性.
结论:
- 细胞内Na+积累是必要的,但不足以完全复制在高盐环境中观察到的增强的巨细胞功能.
- 除了离子干扰外,还需要高血压压力,才能充分增强巨细胞的抗菌活性.
- 心脏糖化物选择性地诱导离子变化,突出显示了离子转移和透应激对巨细胞激活的明显贡献.
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