Freshly isolated bone marrow monocytes from mice lacking βENaC or ASIC2 have sex-linked reduced chemotactic migration responses

Abstract

The monocyte-macrophage system plays an important role in phagocytosis of pathogens and cellular debris following infection or tissue injury. Circulating monocytes differentiate into macrophages which can be polarized into pro- or anti-inflammatory phenotypes. A previous study from our laboratory demonstrated the RAW cell monocyte-macrophage line express α and β Epithelial Na+ Channel (ENaC) subunits which contribute to chemotactic migration and polarization. Here we tested the hypothesis that freshly isolated bone marrow monocytes also express ENaC and related Acid Sensing Ion Channel transcripts which may contribute to monocyte migration. Using qRT-PCR, we found α, βENaC and ASIC1-5 are similarly expressed in freshly isolated bone marrow monocytes from wild-type male and female mice. We also examined chemotactic migration in monocytes isolated from global βENaC hypomorph mice and ASIC2 knockout mice. We found migration was differentially inhibited in male and female animals. In ASIC2−/− monocytes, migration was inhibited to 76±2% and 86±2% of control in male and female animals, respectively. In βENaC hypomorph monocytes, migration was inhibited to 74±2% and 56%±3 of control in male and female animals, respectively. These findings suggest that βENaC and ASIC2 contribute similarly to monocyte migration in males, however, βENaC plays a greater role in migration (than ASIC2) in females. The in-vivo role of βENaC and ASIC2 to monocyte responses associated with inflammation has not been addressed. This research was supported by NIH R01HL136884, P20GM104357, P30GM149404, P20GM121334, and P20GM103476. This is the full abstract presented at the American Physiology Summit 2024 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.