Hepatitis C transmission using lymphocytes as vectors: mechanism and therapeutic interventions and Neutrophil recruitment to microvascular endothelium: the impact of mesenchymal stem cells

Petrovic, Kristina (2014). Hepatitis C transmission using lymphocytes as vectors: mechanism and therapeutic interventions and Neutrophil recruitment to microvascular endothelium: the impact of mesenchymal stem cells. University of Birmingham. M.Res.

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Abstract

Project 1:
Hepatitis C virus (HCV) can be transmitted from B-lymphocytes to hepatocytes – a process termed trans-infection. This project characterised trans-infection further by examining receptors involved in HCV transmission from B- and T-lymphocytes to hepatoma cells. Both lymphocyte classes were equally capable of trans-infection, which was significantly reduced by HCV entry receptor inhibitors or neutralising antibodies. The actin cytoskeleton of the hepatocyte was also involved. Further work is needed to fully characterise HCV trans-infection, which would provide us with crucial insights into the varied modes of HCV transmission.

Project 2:
Neutrophil recruitment to inflamed tissue is essential in physiological and pathological inflammation. Mesenchymal stem cells (MSC) reduce neutrophil adhesion to inflamed macrovascular endothelium, but may become immunostimulatory in chronically inflamed tissue. This project characterised neutrophil recruitment to microvascular endothelium, examined whether MSC could suppress it, and studied MSC phenotype changes on exposure to pro-inflammatory cytokines. Micro- and macrovascular endothelium supported neutrophil adhesion equally well, but MSC suppression of neutrophil recruitment was not observed. Prolonged stimulation with transforming growth factor β in low serum altered MSC surface expression. Further studies of MSC phenotype changes in inflammation and their effect on endothelial neutrophil recruitment may shed light on the complex cellular interactions within chronically inflamed tissue.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):