Damage associated molecular patterns and neutrophil extracellular traps in acute pancreatitis

Abstract

Previous researches have emphasized a trypsin-centered theory of acute pancreatitis (AP) for more than a century. With additional studies into the pathogenesis of AP, new mechanisms have been explored. Among them, the role of immune response bears great importance. Pro-inflammatory substances, especially damage-associated molecular patterns (DAMPs), play an essential role in activating, signaling, and steering inflammation. Meanwhile, activated neutrophils attach great importance to the immune defense by forming neutrophil extracellular traps (NETs), which cause ductal obstruction, premature trypsinogen activation, and modulate inflammation. In this review, we discuss the latest advances in understanding the pathological role of DAMPs and NETs in AP and shed light on the flexible crosstalk between these vital inflammatory mediators. We, then highlight the potentially promising treatment for AP targeting DAMPs and NETs, with a focus on novel insights into the mechanism, diagnosis, and management of AP.

Inflammation and Acinar Cell Dual-Targeting Nanomedicines for Synergistic Treatment of Acute Pancreatitis via Ca2+ Homeostasis Regulation and Pancreas Autodigestion Inhibition

“…During AP, injured PACs commonly release substances from the cell, comprising damage-associated molecular patterns (DAMPs), which trigger diverse immune cells’ recruitment (including neutrophils, monocytes, and macrophages) to the damaged area, inducing cell polarization and release of inflammatory factors and cytokines, thereby activating inflammatory cascade. − …”

Identification of novel biomarkers based on lipid metabolism-related molecular subtypes for moderately severe and severe acute pancreatitis

“…It was found that NMAP patients had greater infiltration ratios of neutrophils and mast cells. Neutrophils were found to be critical in the development of AP, and treatment aimed at neutrophils significantly reduced tissue damage and prevented pancreatitis [ 39 , 40 ]. Mast cells also usually play a key role in the inflammatory reaction in AP [ 41 ], which is consistent with the results we obtained.…”

High expression of P-selectin induces neutrophil extracellular traps via the PSGL-1/Syk/Ca2+/PAD4 pathway to exacerbate acute pancreatitis

“…Clarifying the endogenous mechanisms underlying AP progression could help to clinically treatment and improve prognosis. Besides the classical role of neutrophils, numerous findings suggest that neutrophil-derived NETs play an important role in the pathophysiology of AP ( 8 , 25 – 27 ). Based on the role of P-selectin in neutrophil functions, our study focused on the relationship between the highly expressed P-selectin and NETs in AP and found that in human neutrophils P-selectin is an important stimulus of NETs formation, which is consistent with the findings of Etulain et al.…”