Progress of pyroptosis in acute pancreatitis

[8,9] The non-classic inflammasome pathway mainly involves the direct binding of murine caspase-11 or human caspase-4 or caspase-5 with toxins and lipopolysaccharides on gram-negative bacteria (including Bacillus rotatum, Escherichia coli, and Vibrio cholerae), leading to GSDMD cleavage and the release of its N-terminal domain, and also can indirectly activate the classic NLRP3-ASC-caspase-1 pathway, leading to the processing and release of IL-1β and IL-18. The N-terminal domain oligomerizes on the cell membrane to form a pore with a diameter of 10 to 16 nm, leading to the loss of the cell ion gradient and water influx, after which the cell swells and secretes smaller diameter substrates, such as IL-1β and IL-18. [11,12] The membrane pores formed by the pyroptosis effector GSDMD can release cytoplasmic contents, with the result that inflammasome effectors (such as IL-1, IL-1β, and IL-18) and inflammatory mediators (such as eicosanoid compounds) are released to the extracellular environment, but the membrane pores are small enough to retain organelles and trap bacteria to prevent bacterial spread, thus forming a structure called pore-induced intracellular traps (PITs). PITs maintain the presence of bacteria, coordinate the innate immune response, and complement and scavenger receptors to drive the recruitment of neutrophils, the formation of neutrophil extracellular traps (NETs), or the recruitment of macrophages to engulf and kill the captured bacteria.