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Recent advances in the role of neutrophils and neutrophil extracellular traps in acute pancreatitis

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Abstract

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.

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Acknowledgements

The authors are thankful for the support provided by the National Institute of Health-NIDDK and Sylvester Comprehensive Cancer Centre.

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HMI was supported by the National Institute of Health-NIDDK R01DK093047. RD was supported by the National Institute of Health-NIDDK R01DK093047 and Sylvester Comprehensive Cancer Centre.

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  1. Department of Surgery and Sylvester Comprehensive Cancer Centre, Miller School of Medicine, University of Miami, Miami, FL, USA

    Hassan Mubarak Ishqi & Rajinder Dawra

  2. Department of Radiation Oncology and Sylvester Comprehensive Cancer Centre, Miller School of Medicine, University of Miami, Miami, FL, USA

    Misha Ali

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HMI and MA reviewed the literature and wrote the manuscript. RD conceptualized, reviewed, edited and wrote a part of the manuscript.

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Ishqi, H.M., Ali, M. & Dawra, R. Recent advances in the role of neutrophils and neutrophil extracellular traps in acute pancreatitis. Clin Exp Med 23, 4107–4122 (2023). https://doi.org/10.1007/s10238-023-01180-4

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