NCX1 represents an ionic Na+ sensing mechanism in macrophages

ABSTRACT: Inflammation and infection can trigger local tissue Na+-accumulation. This Na+-rich environment boosts pro-inflammatory activation of monocyte/macrophage-like cells (MΦ) and their antimicrobial activity. Enhanced Na+-driven MΦ-function requires the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5), which augments NO production and contributes to increased autophagy. However, the mechanism of Na+-sensing in MΦ remained unclear. High extracellular Na+ levels (HS) trigger a substantial Na+-influx and Ca2+ loss. Here, we show that the Na+/ Ca2+-exchanger 1 (NCX1/ solute carrier family 8 member A1 (SLC8A1)) plays a critical role in HS-triggered Na+-influx, concomitant Ca2+ efflux and subsequent 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE136662 | GEO | 2020/06/29

REPOSITORIES: GEO