Sodium overload and water influx activate the NALP3 inflammasome.

ABSTRACT: The NALP3 inflammasome is activated by low intracellular potassium concentrations [K(+)](i), leading to the secretion of the proinflammatory cytokine IL-1β. However, the mechanism of [K(+)](i) lowering after phagocytosis of monosodium urate crystals is still elusive. Here, we propose that endosomes containing monosodium urate crystals fuse with acidic lysosomes. The low pH in the phagolysosome causes a massive release of sodium and raises the intracellular osmolarity. This process is balanced by passive water influx through aquaporins leading to cell swelling. This process dilutes [K(+)](i) to values below the threshold of 90 mm known to activate NALP3 inflammasomes without net loss of cytoplasmic potassium ions. In vitro, the inhibitors of lysosomal acidification (ammonium chloride, chlor

SUBMITTER: Schorn C 

PROVIDER: S-EPMC3012992 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature