Necroptosis and neutrophil-associated disorders

Necroptosis is a form of regulated necrosis and is dependent on a signaling pathway involving receptor interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL). Necroptosis is considered to have important functions in inflammation and, based on studies with animal disease models, is believed likely to be involved in the pathogenesis of many human inflammatory diseases. In neutrophils, necroptosis has recently been reported to be triggered by tumor necrosis factor (TNF) stimulation, ligation of adhesion receptors, exposure to monosodium urate (MSU) crystals, or phagocytosis of Staphylococcus aureus (S. aureus). Because neutrophils are involved in many kinds of tissue inflammation and disease, neutrophil necroptosis probably plays a vital role in such processes. Dissecting the signaling pathway of neutrophil necroptotic death may help to identify novel drug targets for inflammatory or autoimmune diseases. In this review, we discuss different mechanisms which regulate neutrophil necroptosis and are thus potentially important in neutrophil-associated disorders.