title: Proposed protective mechanism of the pancreas in the rat.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Sciences Lund, Lund University, BMC, D12, SE-221 84 Lund, Sweden. jakob_b.axelsson@med.lu.se.
authors.forename: Jakob Bf
authors.initials: JB
authors.lastname: Axelsson
authors.forename: Hamid
authors.initials: H
authors.lastname: Akbarshahi
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Said
authors.forename: Anders
authors.initials: A
authors.lastname: Malmström
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson