%0 Journal Article
%T NCX1 represents an ionic Na+ sensing mechanism in macrophages
%A Agnes Schr£¿der
%A Andrea Weichselbaum
%A Anna C. Aschenbrenner
%A Anna-Lorena B£¿r
%A Arne Homann
%A Christian Kurts
%A David Wendelborn
%A Dominik N. M¨¹ller
%A Jens Titze
%A Joachim L. Schultze
%A Jonas Schulte-Schrepping
%A Karin Hammer
%A Karl Kunzelmann
%A Katrina J. Binger
%A Luka Krampert
%A Maximilian Trum
%A Patrick Neubert
%A Peter Linz
%A Roland Veelken
%A Sabrina Geisberger
%A Stefan Ebner
%A Stefan Wagner
%A Thomas Quast
%A Valentin Schatz
%A Waldemar Kolanus
%J PLOS Biology: A Peer-Reviewed Open-Access Journal
%D 2020
%R 10.1371/journal.pbio.3000722
%X Inflammation and infection can trigger local tissue Na+ accumulation. This Na+-rich environment boosts proinflammatory activation of monocyte/macrophage-like cells (M¦µs) and their antimicrobial activity. Enhanced Na+-driven M¦µ 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¦µs 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 M¦µ responses upon HS exposure. Manipulating NCX1 offers a new strategy to regulate M¦µ function
%K Nitric oxide
%K Small interfering RNA
%K Immunoblotting
%K Endotoxins
%K Inflammation
%K Escherichia coli infections
%K Green fluorescent protein
%K Membrane potential
%U https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000722