Figure 2

The pattern of HMGB1 translocation during cell death. Apoptotic cells can retain HMGB1 tightly bound to chromatin in the nucleus, but, during late apoptosis or secondary necrosis, can release this protein; this isoform is oxidized and lacks immunological activity (depicted by red dots). During necrosis, the plasma membrane and nuclear membrane lose integrity, releasing a proinflammatory form of HMGB1 (red stars). During pyroptosis, following inflammasome activation, the plasma membrane opens and HMGB1 release occur (red stars). If, with pyroptosis, TLR activation occurs, a cytokine-inducing form can also be released (not shown). While NETosis also induces inflammation and releases nuclear material, the redox state of the released HMGB1 in this type of cell death is yet unknown (depicted by red circles). The helical symbols indicate DNA. In NETosis, DNA is released in the form of strands or meshes; while the DNA has a high molecular weight with necrosis, it is not organized or associated with cytoplasmic proteins. The blue dots indicate a nucleosome structure. In apoptosis and pyroptosis, the DNA is cleaved (not shown); laddering occurs with apoptosis but not pyroptosis.