Figure 4

Role of intracellular and extracellular HMGB1 in acute pancreatitis. Under normal conditions, HMGB1 is located in the nucleus of pancreatic acinar cells to regulate nucleosome stability. However, under conditions of increased pathologic insult, increased oxidative stress and calcium overload leads to HMGB1 release. Loss of intracellular HMGB1 in pancreatic acinar cells accelerates DNA damage, cell death and nDAMP (for example, histone) release. Subsequently, extracellular histone promotes immune cell (for example, macrophage and neutrophil) recruitment and activation, which leads to HMGB1 release. Consequently, circulating HMGB1 levels are increased and function as a mediator of lethal systemic inflammation in acute pancreatitis.