Bone marrow macrophage migration is dependent on ASIC2 and betaENaC
PHYSIOLOGY(2023)
摘要
Monocyte-macrophages play an important role in phagocytosis of pathogens and cellular debris following infection or tissue injury in several pathophysiological conditions. Naïve macrophages (Mf), can be polarized into proinflammatory (M1), and/or anti-inflammatory (M2) phenotypes. M1 cells are more phagocytic and adhesive/less motile than anti-inflammatory M2 macrophages. A previous study from our laboratory in the RAW monocyte-macrophage cell line suggests that polarization to M1 macrophages involves inhibition of Epithelial Na + Channel (ENaC) expression, leading to loss of motility. To determine if a similar relationship between ENaC and migration exists in bone marrow macrophages (BMM), we examined chemotactic migration in BMMs from mice lacking βENaC and ASIC2a (KO). BMMs were harvested from the femurs of male and female WT and KO mice (6-12 weeks of age), expanded in culture with colony stimulating factor 1 (CSF1, 20 ng/ml) and cryopreserved for later use. Chemotactic migration responses were inhibited in BMM from KO male (94±4 vs 60±2 cells/FOV, n=35-42 FOVs) and female (142±5 vs 74±3 cells/FOV, n=42) mice. ENaC blockade using 1 μM amiloride inhibited migration in WT BMMs equivalent to migration in untreated KO BMMs and had no further inhibitory effect on KO BMM migration. These findings suggest βENaC and/or ASIC2 account for up to 50% of chemotactic migration in BMM and 100% of amiloride-dependent migration. BMM migration responses were rescued in stable transfected male KO BMMs with βENaC (88±4) or ASIC2a (77±5) compared to the EGFP_control KO (60±2 cells/FOV), providing further evidence of the importance of βENaC and/or ASIC2 in BMM migration. Polarization of male BMMs with IFNg (10 ng/mL, 18 hr) inhibited migration in BMM from WT (64±3 vs 22±1 cells/FOV) and KO (48±2 vs 16±1) animals, suggesting KO BMMs do not behave like fully polarized M1 macrophages. Taken together, our findings indicate that βENaC and ASIC2a play an important role in BMM migration response. Loss of βENaC/ASIC2a leads to a low migratory phenotype like M1 macrophages. Restoration of βENaC or ASIC2 rescues BMM migration. Targeting ENaC activity/expression in BMMs may limit their ability to migrate to sites of injury. Whether this is benefical or detrimental to non-infectious tissue injury is unclear. NIH R01HL136684, P20GM104357, and P20GM121334. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
更多查看译文
关键词
bone marrow macrophage migration,bone marrow,asic2,betaenac
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要