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Updated: Feb 19, 2026
Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
Systemic histone release disrupts plasmalemma and contributes to necrosis in acute pancreatitis
Peter Szatmary1, Tingting Liu2, Simon T Abrams3
1NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, L69 3GA, UK; Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, L69 3BX, UK.
Background:
Clinical and experimental acute pancreatitis feature histone release within the pancreas from innate immune cells and acinar cell necrosis. In this study, we aimed to detail the source of circulating histones and assess their role in the pathogenesis of acute pancreatitis.
Methods:
Circulating nucleosomes were measured in patient plasma, taken within 24 and 48 h of onset of acute pancreatitis and correlated with clinical outcomes. Using caerulein hyperstimulation, circulating histones were measured in portal, systemic venous and systemic arterial circulation in mice, and the effects of systemic administration of histones in this model were assessed. The sites of actions of circulating histones were assessed by administration of FITC-labelled histones. The effects of histones on isolated pancreatic acinar cells were further assessed by measuring acinar cell death and calcium permeability in vitro.
Results:
Cell-free histones were confirmed to be abundant in human acute pancreatitis and found to derive from pancreatitis-associated liver injury in a rodent model of the disease. Fluorescein isothianate-labelled histones administered systemically targeted the pancreas and exacerbated injury in experimental acute pancreatitis. Histones induce charge- and concentration-dependent plasmalemma leakage and necrosis in isolated pancreatic acinar cells, independent of extracellular calcium.
Conclusion:
We conclude that histones released systemically in acute pancreatitis concentrate within the inflamed pancreas and exacerbate injury. Circulating histones may provide meaningful biomarkers and targets for therapy in clinical acute pancreatitis.
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