Neubert, Patrick and Homann, Arne and Wendelborn, David and Baer, Anna-Lorena and Krampert, Luka and Trum, Maximilian and Schroeder, Agnes and Ebner, Stefan and Weichselbaum, Andrea and Schatz, Valentin and Linz, Peter and Veelken, Roland and Schulte-Schrepping, Jonas and Aschenbrenner, Anna C. and Quast, Thomas and Kurts, Christian and Geisberger, Sabrina and Kunzelmann, Karl and Hammer, Karin and Binger, Katrina J. and Titze, Jens and Mueller, Dominik N. and Kolanus, Waldemar and Schultze, Joachim L. and Wagner, Stefan and Jantsch, Jonathan (2020) NCX1 represents an ionic Na(+)sensing mechanism in macrophages. PLOS BIOLOGY, 18 (6): e3000722. ISSN 1544-9173, 1545-7885
Full text not available from this repository. (Request a copy)Abstract
Inflammation and infection can trigger local tissue Na(+)accumulation. This Na+-rich environment boosts proinflammatory activation of monocyte/macrophage-like cells (M phi s) and their antimicrobial activity. Enhanced Na+-driven M phi 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 M phi s 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 M phi responses upon HS exposure. Manipulating NCX1 offers a new strategy to regulate M phi function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SODIUM-CALCIUM EXCHANGE; ANTIBACTERIAL DEFENSE; NA+/CA2+ EXCHANGER; CA2+ ENTRY; EXPRESSION; PROTEIN; CELLS; INHIBITOR; AMILORIDE; CHANNELS; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Medicine > Lehrstuhl für Kieferorthopädie Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2021 11:48 |
| Last Modified: | 22 Mar 2021 11:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44471 |
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