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48 Endovascular inflammation may occur via tissue-specific mechanisms
  1. J Giles1,
  2. A Greenhalgh1,
  3. A Denes1,
  4. P Thornton1,
  5. N Rothwell1,
  6. B McColl2,
  7. S Allan1
  1. 1Faculty of Life Sciences, The University of Manchester, Manchester UK
  2. 2The Roslin Institute, University of Edinburgh, Edinburgh UK

Abstract

Invading neutrophils are important contributors to brain injury in the context of ischaemia. In vitro evidence suggests a key role for platelet-derived interleukin-1α in mediating neutrophil migration across the vascular endothelium. The aim of this study was to determine the role of platelets and IL-1 using in vivo models of vascular inflammation. Two murine models were used. Bacterial endotoxin, lipopolysaccharide (LPS), was injected intraperitoneally into C57BL/6 mice and lavage of the peritoneal cavity was performed 6 h later. LPS was stereotactically injected into the striatum, and the brain fixed and removed 24 h later. Flow cytometry was used to assess neutrophil levels in suspension, while immunohistochemistry was used to assess neutrophil numbers in tissue. To determine the role of platelets, platelet depletion was induced by injection of anti-CD41 antibody 24 h prior to LPS. To determine the role of IL-1, IL-1α/β double knockout mice were used. In the peritoneum, platelet depletion abolished neutrophil migration, indicating a key role for platelets in this process. A robust inflammatory response was seen in serum cytokines after LPS injection and platelet depletion selectively abrogated the increase in serum IL-1α. IL-1α/β double knockout mice revealed a significant difference in LPS-induced neutrophil migration between knockout animals and controls in the encephalitis model, with no difference in the peritonitis model. In an in vivo peritonitis model, neutrophil migration appears to be dependent on platelets, yet independent of IL-1. In an encephalitis model, neutrophil migration appears dependent on IL-1. This may suggest differential migration mechanisms in different vascular beds.

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