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| Item Type: | Article |
|---|---|
| Title: | NCX1 represents an ionic Na(+) sensing mechanism in macrophages |
| Creators Name: | Neubert, P., Homann, A., Wendelborn, D., Bär, A.L., Krampert, L., Trum, M., Schröder, A., Ebner, S., Weichselbaum, A., Schatz, V., Linz, P., Veelken, R., Schulte-Schrepping, J., Aschenbrenner, A.C., Quast, T., Kurts, C., Geisberger, S., Kunzelmann, K., Hammer, K., Binger, K.J., Titze, J., Müller, D.N., Kolanus, W., Schultze, J.L., Wagner, S. and Jantsch, J. |
| Abstract: | Inflammation and infection can trigger local tissue Na(+) accumulation. This Na(+)-rich environment boosts proinflammatory activation of monocyte/macrophage-like cells (MΦs) and their antimicrobial activity. Enhanced Na(+)-driven MΦ function requires the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5), which augments nitric oxide (NO) production and contributes to increased autophagy. However, the mechanism of Na(+) sensing in MΦs remained unclear. High extracellular Na(+) levels (high salt [HS]) trigger a substantial Na(+) influx and Ca(2+) loss. Here, we show that the Na(+)/Ca(2+) exchanger 1 (NCX1, also known as solute carrier family 8 member A1 [SLC8A1]) plays a critical role in HS-triggered Na(+) influx, concomitant Ca(2+) efflux, and subsequent augmented NFAT5 accumulation. Moreover, interfering with NCX1 activity impairs HS-boosted inflammatory signaling, infection-triggered autolysosome formation, and subsequent antibacterial activity. Taken together, this demonstrates that NCX1 is able to sense Na+ and is required for amplifying inflammatory and antimicrobial MΦ responses upon HS exposure. Manipulating NCX1 offers a new strategy to regulate MΦ function. |
| Keywords: | Alternative Splicing, Calcium, Extracellular Space, Gene Silencing, Ion Channel Gating, Ions, Lipopolysaccharides, Macrophages, Nitric Oxide, RAW 264.7 Cells, Sodium, Sodium Chloride, Sodium-Calcium Exchanger, Animals, Mice |
| Source: | PLoS Biology |
| ISSN: | 1544-9173 |
| Publisher: | Public Library of Science |
| Volume: | 18 |
| Number: | 6 |
| Page Range: | e3000722 |
| Date: | 22 June 2020 |
| Official Publication: | https://doi.org/10.1371/journal.pbio.3000722 |
| PubMed: | View item in PubMed |
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