NCX1 represents an ionic Na+ sensing mechanism in macrophages
Neubert P, Homann A, Wendelborn D, Bär AL, Krampert L, Trum M, Schröder A, Ebner S, Weichselbaum A, Schatz V, Linz P, Veelken R, Schulte-Schrepping J, Aschenbrenner AC, Quast T, Kurts C, Geisberger S, Kunzelmann K, Hammer K, Binger KJ, Titze J, Müller DN, Kolanus W, Schultze JL, Wagner S, Jantsch J (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 18
Pages Range: e3000722-
Journal Issue: 6
DOI: 10.1371/journal.pbio.3000722
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 Ca2+ loss. Here, we show that the Na+/Ca2+ exchanger 1 (NCX1, also known as solute carrier family 8 member A1 [SLC8A1]) plays a critical role in HS-triggered Na+ influx, concomitant Ca2+ 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.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Regensburg
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Universität Regensburg
Germany (DE)
La Trobe University
Australia (AU)
Duke-NUS Medical School / 杜克—国大医学研究生院
Singapore (SG)
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Universität Regensburg
Germany (DE)
La Trobe University
Australia (AU)
Duke-NUS Medical School / 杜克—国大医学研究生院
Singapore (SG)
How to cite
APA:
Neubert, P., Homann, A., Wendelborn, D., Bär, A.L., Krampert, L., Trum, M.,... Jantsch, J. (2020). NCX1 represents an ionic Na+ sensing mechanism in macrophages. Plos Biology, 18(6), e3000722-. https://doi.org/10.1371/journal.pbio.3000722
MLA:
Neubert, Patrick, et al. "NCX1 represents an ionic Na+ sensing mechanism in macrophages." Plos Biology 18.6 (2020): e3000722-.
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