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Heparin Binding Protein and the Glycocalyx in Sepsis

Fisher, Jane (2016) MOBT01 20161
Degree Projects in Molecular Biology
Popular Abstract
Sepsis is a severe and often lethal inflammatory response to an infection. During sepsis the cells and organs no longer function as they should because of the intense immune response. Some of the cell dysfunction may be because of an important “sugar layer” known as the glycocalyx. In this study, we determined whether an inflammatory protein, heparin binding protein (HBP), might contribute to the disruption of the glycocalyx in sepsis.

Background
HBP is a pro-inflammatory protein from neutrophils which is associated with, and may also cause, kidney and lung injury in sepsis. How HBP can cause kidney and lung injury is not known, but it has been suggested that the glycocalyx may be important. The glycocalyx is a layer of sugar chains... (More)
Sepsis is a severe and often lethal inflammatory response to an infection. During sepsis the cells and organs no longer function as they should because of the intense immune response. Some of the cell dysfunction may be because of an important “sugar layer” known as the glycocalyx. In this study, we determined whether an inflammatory protein, heparin binding protein (HBP), might contribute to the disruption of the glycocalyx in sepsis.

Background
HBP is a pro-inflammatory protein from neutrophils which is associated with, and may also cause, kidney and lung injury in sepsis. How HBP can cause kidney and lung injury is not known, but it has been suggested that the glycocalyx may be important. The glycocalyx is a layer of sugar chains called glycosaminoglycans (GAGs) attached to proteins called proteoglycans, which protects cells and regulates many of their functions. Syndecan-1 to 4 and glypican-1 to 6 are the major proteoglycans on the cell surface. Syndecan-1 and GAGs in the plasma are associated with endothelial damage in sepsis, but plasma glypicans in sepsis have never been explored.

Results
Mice which were injected with HBP showed visible signs of bleeding and inflammation in the kidneys and lungs, suggesting that HBP can cause kidney and lung injury. HBP also altered the level of certain syndecans and glypicans on the surface of cultured human kidney cells and increased their release from cultured human endothelial cells. This indicates that HBP could disrupt the composition, and therefore the function, of the glycocalyx contributing to kidney and lung injury in sepsis on a cellular level.

Syndecan-4 was found to specifically localize with HBP, and its presence on the cells was necessary for HBP-induced changes in glypican-4 levels. Therefore syndecan-4 could act as a receptor for HBP, providing a possible therapeutic target for blocking HBP in sepsis.

Lastly, the plasma level of glypican-1, 3 and 4 was associated with the severity of sepsis in a study of 202 patients. This is the first time that glypicans have been associated with sepsis and indicates that glypicans should be explored further as possible markers of damage in sepsis.

Advisor: Adam Linder
Master´s Degree Project 60 credits in Molecular Biology, 2016
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Fisher, Jane
supervisor
organization
course
MOBT01 20161
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8891607
date added to LUP
2016-09-13 14:45:11
date last changed
2016-09-13 14:45:11
@misc{8891607,
  author       = {Fisher, Jane},
  language     = {eng},
  note         = {Student Paper},
  title        = {Heparin Binding Protein and the Glycocalyx in Sepsis},
  year         = {2016},
}