Enzyme load in pancreatic acinar cells is increased in the early stages of acute pancreatitis induced by duct obstruction in rats

2000 ◽  
Vol 98 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Aránzazu URUÑUELA ◽  
Manuel A. MANSO ◽  
Rosa M PINTO ◽  
Alberto ORFAO ◽  
Isabel DE DIOS
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cells ◽  
Enzyme Synthesis ◽  
Pancreatic Acinar Cells ◽  
Intracellular Enzyme ◽  
Duct Obstruction ◽  
Early Stages ◽  
Morphological Studies ◽  
Pancreatic Duct Obstruction ◽  
Enzyme Load

Trypsinogen and amylase content has been analysed by flow cytometry in individual pancreatic cells from rats with acute pancreatitis induced by pancreatic duct obstruction, from the earliest stages to 48 h after obstruction. Parallel morphological studies of the pancreas by electron microscopy and analysis of various parameters for the diagnosis of pancreatitis will allow research into the possible relationship between intracellular enzyme load and the severity of pancreatitis. Progressive increases in amylase activity in ascites and plasma, the volume of ascites, haematocrit, vacuolization, oedema and macrophage infiltration were observed between 1.5 h and 12 h after duct obstruction. A progressive increase in enzyme content was also observed in individual acinar cells at this stage. Interestingly, the larger increase was for trypsinogen, so that the trypsinogen/amylase ratio was significantly increased in all acinar cells by 12 h after duct obstruction. This represents a risk factor for the development of pancreatitis. Sections of pancreas taken from rats that had duct obstruction for 48 h showed massive dilatation and disorganization of the endoplasmic reticulum, focal apoptosis and necrosis. These severe alterations would affect enzyme synthesis, as reflected by the significant decrease in the intracellular enzyme load observed at this stage. However, not all acinar cells were affected equally by the damage induced by pancreatitis: R1 cells appeared to be more sensitive than R2 cells. In conclusion, intracellular accumulation of digestive enzymes occurs at early stages of pancreatitis, and this effect is proportionally greater for trypsinogen, a finding that could explain the degree of severity achieved in the course of pancreatitis.

Enzyme load in pancreatic acinar cells is increased in the early stages of acute pancreatitis induced by duct obstruction in rats

2000 ◽  
Vol 98 (2) ◽  
pp. 143 ◽  
Author(s):  
Aránzazu URUÑUELA ◽  
Manuel A. MANSO ◽  
Rosa Ma PINTO ◽  
Alberto ORFAO ◽  
Isabel DE DIOS
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Duct Obstruction ◽  
Early Stages ◽  
Enzyme Load

Asynchronous impairment of calcium homoeostasis in different acinar cells after pancreatic duct obstruction in rat

2002 ◽  
Vol 102 (6) ◽  
pp. 615-622 ◽  
Author(s):  
Aránzazu URUÑUELA ◽  
Manuel A. MANSO ◽  
Ana Ma DE LA MANO ◽  
Sara SEVILLANO ◽  
Alberto ORFAO ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Pancreatitis ◽  
Pancreatic Duct ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Current Evidence ◽  
Duct Obstruction ◽  
Morphological Alterations ◽  
Pancreatic Duct Obstruction ◽  
Severity Of The Disease

Current evidence suggests that alterations within acinar cells are responsible for the development of acute pancreatitis. After inducing acute pancreatitis in rats by pancreatic duct obstruction, we analysed, using flow cytometry, the progressive changes in cytosolic Ca2+ concentrations in individual acinar cells from the earliest stages to 48h after obstruction to investigate whether parallel alterations in the homoeostasis of Ca2+ could be defined in the different acinar cells throughout the evolution of pancreatitis. Morphological alterations of the pancreas, related to the severity of the disease at different stages, were observed by electron microscopy. Hyperamylasaemia and progressively more severe alterations, such as vacuolization, dilatation of endoplasmic reticulum, accumulation of zymogen granules and reorientation towards basolateral membrane, were observed during the first 12h after pancreatic obstruction. A significant increase in cytosolic Ca2+ concentration was measured at these stages in a particular type of acinar cells (R1) differentiated by flow cytometry with low forward scatter (FSC), whereas another representative group of cells (R2) with higher FSC values were able to maintain resting cytosolic Ca2+ concentrations up to 24h after obstruction. Longer periods of pancreatic duct obstruction induced disturbances in Ca2+ homoeostasis in all acinar cells. A similar increase in cytosolic Ca2+ load was reached in both R1 and R2 cells when acute pancreatitis was completely developed. In conclusion, the homoeostasis of Ca2+ in acinar cells is asynchronously impaired during the development of acute pancreatitis; cells with higher FSC (R2) appear to be more resistant than R1 cells.

Cholecystokinin blockade triggers earlier and enhanced intra-acinar oxygen free radical generation in acute pancreatitis induced by pancreatic duct obstruction in rats

2003 ◽  
Vol 105 (2) ◽  
pp. 203-212 ◽  
Author(s):  
Aránzazu URUÑUELA ◽  
Manuel A. MANSO ◽  
Ana M. DE LA MANO ◽  
Isabel DE DIOS
Keyword(s):  
Flow Cytometry ◽  
Acute Pancreatitis ◽  
Free Radical ◽  
Pancreatic Duct ◽  
Severe Disease ◽  
Acinar Cells ◽  
Oxygen Free Radical ◽  
Duct Obstruction ◽  
Pancreatic Duct Obstruction ◽  
Cck Antagonist

Cholecystokinin (CCK) has been suggested to be a contributory mediator in acute pancreatitis (AP). The aim of the present study was to assess the role of CCK in the development of oxidative stress at different stages of AP induced by pancreatic duct obstruction (PDO) in rats, using L364,718 (a potent CCK-receptor antagonist) to block CCK action. Intra-acinar oxygen free radical (OFR) generation was analysed by flow cytometry using dihydrorhodamine-123 as a fluorogenic dye. Parallel measurements of pancreatic levels of reduced glutathione (GSH) and of several parameters for the diagnosis of AP were performed in both untreated PDO rats and PDO rats receiving L364,718 (0.1 mg·12 h-1·kg-1). Diagnosis parameters indicated a greater severity of AP in rats treated with the CCK antagonist. The increase in OFR generation observed in acinar cells up to 12 h after inducing AP was triggered at an earlier stages and reached higher values when L364,718 was administered. Accordingly, greater pancreatic GSH depletion was observed in rats with AP treated with the CCK antagonist. Two populations of acinar cells that were differentiated by flow cytometry, R1 and R2, showed similar behaviour with regard to OFR generation in PDO rats; however, R1 cells showed greater sensitivity to L364,718 administration, and thus OFR production was increased in R1 cells earlier than in R2 cells. In conclusion, CCK blockade anticipates and enhances the amount of OFR produced in acinar cells as a consequence of AP, thus leading to earlier development of and more severe disease. The detrimental effect of L364,718 in AP induced by PDO suggests that plasma CCK does not play a major role in the development of this AP model.

scholarly journals Absence of the neutrophil serine protease cathepsin G decreases neutrophil granulocyte infiltration but does not change the severity of acute pancreatitis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ali A. Aghdassi ◽  
Daniel S. John ◽  
Matthias Sendler ◽  
Christian Storck ◽  
Cindy van den Brandt ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Serine Protease ◽  
Acinar Cells ◽  
Neutrophil Infiltration ◽  
Cathepsin G ◽  
Pancreatic Acinar Cells ◽  
Neutrophil Granulocyte ◽  
Zymogen Activation ◽  
Trypsinogen Activation ◽  
Extracellular Matrix Components

AbstractAcute pancreatitis is characterized by an early intracellular protease activation and invasion of leukocytes into the pancreas. Cathepsins constitute a large group of lysosomal enzymes, that have been shown to modulate trypsinogen activation and neutrophil infiltration. Cathepsin G (CTSG) is a neutrophil serine protease of the chymotrypsin C family known to degrade extracellular matrix components and to have regulatory functions in inflammatory disorders. The aim of this study was to investigate the role of CTSG in pancreatitis. Isolated acinar cells were exposed to recombinant CTSG and supramaximal cholezystokinin stimulation. In CTSG−/− mice and corresponding controls acute experimental pancreatitis was induced by serial caerulein injections. Severity was assessed by histology, serum enzyme levels and zymogen activation. Neutrophil infiltration was quantified by chloro-acetate ersterase staining and myeloperoxidase measurement. CTSG was expessed in inflammatory cells but not in pancreatic acinar cells. CTSG had no effect on intra-acinar-cell trypsinogen activation. In CTSG−/− mice a transient decrease of neutrophil infiltration into the pancreas and lungs was found during acute pancreatitis while the disease severity remained largely unchanged. CTSG is involved in pancreatic neutrophil infiltration during pancreatitis, albeit to a lesser degree than the related neutrophil (PMN) elastase. Its absence therefore leaves pancreatitis severity essentially unaffected.

TRANSCRIPTION FACTOR PROFILING OF PANCREATIC ACINAR CELLS FOLLOWING TNF-α INDUCTION OF ACUTE PANCREATITIS.

Shock ◽  
2003 ◽  
Vol 19 (Supplement) ◽  
pp. 20
Author(s):  
L. Vona-Davis ◽  
K. Magabo ◽  
B. Jackson ◽  
T. Evans ◽  
D. Riggs ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Transcription Factor ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Tnf Α

Acinar Akt1 in pancreatic acinar cells supports proliferation and limits acinar-to-ductal metaplasia formation upon induction of acute pancreatitis

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S101
Author(s):  
Rong Chen ◽  
Ermanno Malagola ◽  
Maren Dietrich ◽  
Richard Zuellig ◽  
Marta Bombardo ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Acinar To Ductal Metaplasia
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