Proposed protective mechanism of the pancreas in the rat

Jakob Bf Axelsson,Katarzyna Said,Roland Andersson,Hamid Akbarshahi,Anders Malmström

doi:10.1186/1476-9255-7-24

Abstract

BackgroundHeparan 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.MethodsRats 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.ResultsDuring 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.ConclusionsOur 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.

Highlights

Heparan sulphate is known to have various functions in the animal body, including surveillance of tissue integrity
Upon closer inspection of which cell types are present in the infiltrate, we found monocytes and neutrophils to be the dominant cell species
To elucidate the mechanism initiating these events we have studied the synthesis of chemoattractants for monocytes and neutrophils (MCP-1 and cytokine-induced neutrophil chemoattractant-1 (CINC-1), respectively) and the following infiltration pattern of these two, for the innate immune response, very important cell types

Summary

Introduction

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. Heparan sulphate proteoglycans (HSPGs) substituted with polysaccharides sulphated to different degrees are found anchored in the plasma membrane of epithelial cells in the pancreas. These PGs have been suggested to represent signaling molecules of membrane integrity [3] by eliciting an inflammatory response in their soluble form, making them candidates of these protective signaling events. Pancreatic enzymes may make HS available for binding to receptors and other biological actions otherwise not available when bound to the epithelial wall [4]

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