Initiation of acute pancreatitis by heparan sulphate in the rat.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Axelsson
Jakob
J
Department of Clinical Sciences, Lund University, Lund, Sweden.
Norrman
Gustav
G
Malmström
Anders
A
Weström
Björn
B
Andersson
Roland
R
D000208:Acute Disease; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D006497:Heparan Sulfate / Q000502:physiology; D015850:Interleukin-6; D008297:Male; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013657:Taurodeoxycholic Acid
D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D006497:Heparan Sulfate; D015850:Interleukin-6; D009195:Peroxidase; D013657:Taurodeoxycholic Acid; C513297:Cxcl1 protein, rat