Plasma membrane permeabilization following cell death: many ways to dye!
Elke De Schutter, Benjamin Cappe, Bartosz Wiernicki, Peter Vandenabeele, Franck B. Riquet
Abstract
In essence, apoptosis is a containment program preparing the cell corpse for engulfment by efferocytosis. When the phagocytic capacity is insufficient, apoptotic cells undergo disintegration accompanied by the release of cellular content, coined secondary necrosis. As secondary necrotic cells can elicit an inflammatory response [ 1 ], insights into the underlying mechanisms or molecules driving secondary necrosis are of major importance for therapeutic targeting. Rogers et al. reported that gasdermin E (GSDME), a member of the pore-forming gasdermin protein family and a substrate of the apoptotic caspase-3, drives secondary necrosis [ 2 ]. Indeed, Gsdme −/− macrophages displayed lower plasma membrane permeabilization upon the stimulation with etoposide, an apoptosis inducer, as assessed by propidium iodide (PI) [ 2 ]. However, other reports showed that the loss of GSDME did not result in differential kinetics in plasma membrane permeabilization measured by TO-PRO-3 fluorescent DNA dye in UV irradiated THP-1 and Jurkat T cells [ 3 ]. Similarly, the absence of GSDME did not affect membrane permeabilization measured by YOYO-1 fluorescent DNA dye in macrophages upon anti-Fas treatment [ 4 ].