Pancreatic stellate cells (PSCs) are thought to be responsible for pancreatic fibrosis. Although fibrosis is a major characteristic of chronic pancreatitis (CP) induced by pancreatic duct obstruction, it is unclear whether pancreatic duct obstruction itself activates PSCs.
To test the hypothesis that pancreatic duct obstruction activates PSCs, clinical and experimental analyses were performed using alpha smooth muscle actin (alpha-SMA) as a marker of their activation. In clinical analysis, surgical specimens from the patients with pancreatic cancer or cancer of the papilla Vater were classified into two groups with or without duct obstruction. alpha-SMA expression was examined on these specimens, and the difference between two groups was evaluated. In animal experiment, duct ligation-induced pancreatitis was developed in rats by ligating the secondary pancreatic duct in duodenal segment, and the expression of alpha-SMA was examined.
In clinical analysis, the specimens from the pancreas with duct obstruction (14 cases) expressed alpha-SMA significantly stronger than those from the pancreas without duct obstruction (7 cases). All specimens in the former expressed alpha-SMA, but 4 specimens from the latter did not at all (P < 0.05). In animal experiment, alpha-SMA expression was detected 7 days after the ligation and was increased on the 10th day.
We can assume that pancreatic duct obstruction itself activates PSCs. This mechanism may play roles in the development of CP from multiple origins.
[Show abstract][Hide abstract] ABSTRACT: Pancreatic stellate cells (PaSCs) are myofibroblast-like cells found in the areas of the pancreas that have exocrine function. PaSCs are regulated by autocrine and paracrine stimuli and share many features with their hepatic counterparts, studies of which have helped further our understanding of PaSC biology. Activation of PaSCs induces them to proliferate, to migrate to sites of tissue damage, to contract and possibly phagocytose, and to synthesize ECM components to promote tissue repair. Sustained activation of PaSCs has an increasingly appreciated role in the fibrosis that is associated with chronic pancreatitis and with pancreatic cancer. Therefore, understanding the biology of PaSCs offers potential therapeutic targets for the treatment and prevention of these diseases.
[Show abstract][Hide abstract] ABSTRACT: The initiating events in the onset of pancreatitis are poorly understood. Possible candidates may be endogenous ligands, acting on receptors within ductal, acinar or stellate cells, which have previously been shown to cause a systemic inflammatory response syndrome. The aim of this study was to investigate whether acute pancreatitis could be induced by heparan sulphate (HS)infused into the pancreatic ducts in the rat.
Retrograde biliary-pancreatic infusion of heparan sulphate of different structures, taurodeoxycholate (TDC) or phosphate buffered saline (PBS) was performed. Local pancreatic inflammation was evaluated after 6 h by means of morphological evaluation, neutrophil and macrophage infiltration and levels of plasma amylase. Systemic inflammation was evaluated by measuring plasma IL-6, MCP-1 and CINC-1 concentrations.
Heparan sulphate induced a local inflammatory response visualized as a rapid infiltration of neutrophils and macrophages into the pancreas. Heparan sulphate induced inflammation and oedema without causing damage to acinar cells, as measured by morphological changes and plasma amylase concentrations. Furthermore, an increase in serum concentrations of CINC-1 and IL-6 was seen. The positive control (TDC) had increased levels of all variables analysed and the negative control (heparan sulphate administered intraperitoneally) was without effects.
Our findings suggest a receptor-mediated innate immune response of the pancreatic cells induced by heparan sulphate. This finding may be helpful in elucidating some of the mechanisms involved during the initiation of pancreatitis, as well as in the search for a potential future therapeutic application.
[Show abstract][Hide abstract] ABSTRACT: Heparan sulphate is known to have various functions in the animal body, including surveillance of tissue integrity. Administered intraperitoneally, it induces a systemic inflammatory response syndrome and when given locally in the pancreas it initiates a protective inflammatory response. The aim of the present study was to investigate the underlying mechanisms behind cell recruitment following intra-ductal infusion of heparan sulphate.
Rats were subjected to intraductal-infusion of heparan sulphate, lipopolysaccharide and phosphate buffered saline into the pancreas. Pancreatic tissue was harvested 1, 3, 6, 9 or 48 hours after infusion and stained immunohistochemically for myeloperoxidase, ED-1, CINC-1 and MCP-1, as well as using eosin hematoxylin staining. Furthermore, MPO activity and MCP-1 and CINC-1 concentrations of tissue homogenates were measured. All differences were analyzed statistically using the Mann-Whitney U-test.
During HS infusion, a rapid influx of macrophages/monocytes, as visualized as ED-1 positive cells, was seen reaching a maximum at 6 hours. After 48 hours, the same levels of ED-1 positive cells were noted in the pancreatic tissue, but with different location and morphology. Increased neutrophil numbers of heparan sulphate treated animals compared to control could be detected only 9 hours after infusion. The number of neutrophils was lower than the number of ED-1 positive cells. On the contrary, LPS infusion caused increased neutrophil numbers to a larger extent than heparan sulphate. Furthermore, this accumulation of neutrophils preceded the infiltration of ED-1 positive cells. Chemokine expression correlates very well to the cell infiltrate. MCP-1 was evident in the ductal cells of both groups early on. MCP-1 preceded monocyte infiltration in both groups, while the CINC-1 increase was only noticeable in the LPS group.
Our data suggest that heparan and LPS both induce host defense reactions, though by using different mechanisms of cell-recruitment. This implies that the etiology of pancreatic inflammation may influence how the subsequent events will develop.
Journal of Inflammation 05/2010; 7(1):24. DOI:10.1186/1476-9255-7-24 · 2.02 Impact Factor
Brian B Haab, Ying Huang, Seetharaman Balasenthil, Katie Partyka, Huiyuan Tang, Michelle Anderson, Peter Allen, Aaron Sasson, Herbert Zeh, Karen Kaul, [...], Marshall Bern, Richard Kwon, Ivan Blasutig, Sudhir Srivastava, Marsha L Frazier, Subrata Sen, Michael A Hollingsworth, Jo Ann Rinaudo, Ann M Killary, Randall E Brand
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.