The release of danger signals from damaged or infected cells leads to the recruitment of leukocytes to the inflammed site. In Cell, Enyedi et al. show that tissue hypo-osmolarity can trigger the release of danger signals. Osmotic swelling induces biophysical changes in the nuclear envelope, including alterations in the nuclear lamin and actin cytoskeleton, that cause translocation and activation of the phospholipase enzyme PLA2. Both nuclear swelling and calcium flux are required for activation of PLA2. This response leads to release of archidonic acid from the nuclear membrane and its oxidation to proinflammatory lipid mediators by 5-lipoxygenase. These findings suggest that nuclear-membrane tension acts as a sensor of osmolarity that, when perturbed, is perceived as a danger signal and results in the release of chemoattractants.

Cell 165, 1160–1170 (2016)