Murine pancreatic duct ligation induces stress kinase activation, acute pancreatitis, and acute lung injury

Meyerholz, David K.; Williard, Deborah E.; Grittmann, Ana-Maria; Samuel, Isaac

doi:10.1016/j.amjsurg.2008.07.009

Cited by 17 publications

(23 citation statements)

References 37 publications

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“…5). We have previously shown activation of ERK mitogen-activated protein (MAP) kinase in the pancreas and lung in ligation-induced acute pancreatitis in mice [3]; here we have detected ERK MAP kinase activation within 1 h of PD ligation in the kidney and the liver (fig. 5).…”

Section: Resultsmentioning

confidence: 50%

“…In our previous study of early ligation-induced acute pancreatitis in mice, the death of a few mice between 24 and 48 h was an unexpected finding [3]. We undertook the present study to clarify whether the observed mortality was reproducible and to investigate its possible causes.…”

Section: Resultsmentioning

confidence: 99%

“…Immunohistochemistry was performed for polymorphonuclear leukocytes (PMN), as described previously [3] (rabbit anti-myeloperoxidase, cat. No.…”

Section: Methodsmentioning

confidence: 99%

“…Selected specimens were subjected to immunohistochemistry for myeloperoxidase (MPO). All morphological and morphometric analyses were performed blinded by an independent pathologist, Dr. Meyerholz (Director, Comparative Pathology Laboratory, University of Iowa), as described previously [3]. …”

Section: Methodsmentioning

confidence: 99%

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A Novel Model of Severe Gallstone Pancreatitis: Murine Pancreatic Duct Ligation Results in Systemic Inflammation and Substantial Mortality

et al. 2010

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Background: Suitable experimental models of gallstone pancreatitis with systemic inflammation and mortality are limited. We developed a novel murine model of duct-ligation-induced acute pancreatitis associated with multiorgan dysfunction and severe mortality. Methods: Laparotomy was done on C57/BL6 mice followed by pancreatic duct (PD) ligation, bile duct (BD) ligation without PD ligation, or sham operation. Results: Only mice with PD ligation developed acute pancreatitis and had 100% mortality. Pulmonary compliance was significantly reduced after PD ligation but not BD ligation. Bronchoalveolar lavage fluid neutrophil count and interleukin-1β concentration, and the plasma creatinine level, were significantly elevated with PD ligation but not BD ligation. Pancreatic nuclear factor ĸB (p65) and activator protein 1 (c-Jun) were activated within 1 h of PD ligation. Conclusion: PD-ligation-induced acute pancreatitis in mice is associated with systemic inflammation, acute lung injury, multiorgan dysfunction and death. The development of this novel model is an exciting and notable advance in the field.

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Section: Resultsmentioning

confidence: 50%

Section: Resultsmentioning

confidence: 99%

“…Immunohistochemistry was performed for polymorphonuclear leukocytes (PMN), as described previously [3] (rabbit anti-myeloperoxidase, cat. No.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

A Novel Model of Severe Gallstone Pancreatitis: Murine Pancreatic Duct Ligation Results in Systemic Inflammation and Substantial Mortality

et al. 2010

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“…As beta cell proliferation was markedly reduced in E1-DN mice in the other two models studied, this suggests that the mechanisms of beta cell proliferation are fundamentally different in the pancreatic duct ligation model from those in the more physiological models of insulin resistance. Ligation of the pancreatic duct leads to acute strong inflammation [46], which induces rapid beta cell mass expansion within days. Based on these results it appears that the 'cytokine storm' in the inflamed ligated pancreas is able to induce the regenerative response without an intact EGFR-signalling pathway.…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor (EGF)-receptor signalling is needed for murine beta cell mass expansion in response to high-fat diet and pregnancy but not after pancreatic duct ligation

et al. 2011

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Aims/hypothesis Epidermal growth factor receptor (EGFR) signalling is essential for the proper fetal development of pancreatic islets and in the postnatal formation of an adequate beta cell mass. In this study we investigated the role of EGFR signalling in the physiological states of beta cell mass expansion in adults during metabolic syndrome and pregnancy, as well as in regeneration after pancreatic duct ligation. Methods Heterozygous Pdx1-EGFR-dominant-negative (E1-DN) mice, which have a kinase-negative EGFR under the Pdx1 promoter, and wild-type mice were both subjected to a high-fat diet, pregnancy and pancreatic duct ligation. Results The beta cell mass of wild-type mice fed the highfat diet increased by 70% and the mice remained normoglycaemic; the E1-DN mice became diabetic and failed to show any compensatory beta cell mass expansion. Similarly, pregnant wild-type mice had four times more proliferating beta cells and a 75% increase in beta cell mass at mid-gestation, in contrast to the pregnant E1-DN mice, which did not show any significant beta cell compensation and were hyperglycaemic in an intraperitoneal glucose tolerance test. However, after pancreatic duct ligation, both the wild-type and E1-DN mice showed similar expression of Ngn3 (also known as Neurog3) and beta cell proliferation increased to a similar level in the ligated part of pancreas. Conclusions/interpretations EGFR signalling is essential in beta cell mass expansion during a high-fat diet and pregnancy where replication is the primary mechanism for compensatory beta cell mass expansion. In contrast, EGFR signalling appears not to be crucial to increased beta cell proliferation after pancreatic duct ligation.

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Ultrastructure of Acinar Cell Injuries in Experimental Acute Pancreatitis Created by Common Bile Duct Ligation

et al. 2011

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Morphogenesis of acute pancreatitis induced by ligation of the common bile duct and the ultrastructure of autolytic transformations of acinar cells were studied. Autolytic changes in acinar cells started from the basal zones and then involved the apical zones. Violation of the zymogen granules integrity, interactions of their contents with the adjacent ultrastructures, destruction (melting) of ultrastructures, and formation of huge autophagosomes play an important role in the development of autolysis. Disordered secretion of zymogen granules (foci of their accumulation in the apical zone), hyperplasia and hypertrophy of centroacinar cells and ductal epitheliocytes aimed at restoration of the pancreatic secretion discharge pathways were seen in the retained acini.

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Murine pancreatic duct ligation induces stress kinase activation, acute pancreatitis, and acute lung injury

Cited by 17 publications

References 37 publications

A Novel Model of Severe Gallstone Pancreatitis: Murine Pancreatic Duct Ligation Results in Systemic Inflammation and Substantial Mortality

A Novel Model of Severe Gallstone Pancreatitis: Murine Pancreatic Duct Ligation Results in Systemic Inflammation and Substantial Mortality

Epidermal growth factor (EGF)-receptor signalling is needed for murine beta cell mass expansion in response to high-fat diet and pregnancy but not after pancreatic duct ligation

Ultrastructure of Acinar Cell Injuries in Experimental Acute Pancreatitis Created by Common Bile Duct Ligation

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