Department of Surgery and Sylvester Comprehensive Cancer Centre, Miller School of Medicine, University of Miami, Miami, FL, USA.
Department of Radiation Oncology and Sylvester Comprehensive Cancer Centre, Miller School of Medicine, University of Miami, Miami, FL, USA.
Clin Exp Med. 2023 Dec;23(8):4107-4122. doi: 10.1007/s10238-023-01180-4. Epub 2023 Sep 19.
Pancreatitis is an inflammatory disease, which is triggered by adverse events in acinar cells of the pancreas. After the initial injury, infiltration of neutrophils in pancreas is observed. In the initial stages of pancreatitis, the inflammation is sterile. It has been shown that the presence of neutrophils at the injury site can modulate the disease. Their depletion in experimental animal models of the acute pancreatitis has been shown to be protective. But information on mechanism of contribution to inflammation by neutrophils at the injury site is not clear. Once at injury site, activated neutrophils release azurophilic granules containing proteolytic enzymes and generate hypochlorous acid which is a strong microbicidal agent. Additionally, emerging evidence shows that neutrophil extracellular traps (NETs) are formed which consist of decondensed DNA decorated with histones, proteases and granular and cytosolic proteins. NETs are considered mechanical traps for microbes, but there is preliminary evidence to indicate that NETs, which constitute a special mechanism of the neutrophil defence system, play an adverse role in pancreatitis by contributing to the pancreatic inflammation and distant organ injury. This review presents the overall current information about neutrophils and their role including NETs in acute pancreatitis (AP). It also highlights current gaps in knowledge which should be explored to fully elucidate the role of neutrophils in AP and for therapeutic gains.
胰腺炎是一种炎症性疾病，由胰腺腺泡细胞的不良事件引发。在初始损伤后，观察到胰腺中中性粒细胞的浸润。在胰腺炎的初始阶段，炎症是无菌的。已经表明，损伤部位中性粒细胞的存在可以调节疾病。在急性胰腺炎的实验动物模型中，已证明耗尽中性粒细胞具有保护作用。但是，关于中性粒细胞在损伤部位对炎症的贡献的机制信息尚不清楚。一旦到达损伤部位，活化的中性粒细胞释放含有蛋白水解酶的嗜天青颗粒，并产生次氯酸，次氯酸是一种强大的杀菌剂。此外，新出现的证据表明，形成了中性粒细胞细胞外陷阱（NETs），其由带有组蛋白、蛋白酶和颗粒和细胞质蛋白的去凝聚 DNA 组成。NETs 被认为是微生物的机械陷阱，但有初步证据表明，NETs 构成了中性粒细胞防御系统的一种特殊机制，通过促进胰腺炎症和远处器官损伤，在胰腺炎中发挥不利作用。这篇综述介绍了关于中性粒细胞及其包括 NETs 在急性胰腺炎（AP）中的作用的最新信息。它还强调了目前知识空白，应该探索这些空白以充分阐明中性粒细胞在 AP 中的作用，并获得治疗收益。
