UNIVERSITY OF MALTA
LIFE SCIENCE RESEARCH SEMINARS
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Investigating the monocyte transcriptome
Rosienne Farrugia
Department of Haematology, University of Cambridge
0044 1223 54 8131
rf270@cam.ac.uk
27th November 2006
(approximately 200-250 words)
Abstract
The initiation phase of atherosclerotic lesion formation is characterised by the recruitment of
monocytes and T-lymphocytes to sites of inflammation in the vessel wall. Adhesion
molecules expressed on the surface of activated platelets and endothelial cells mediate
monocyte adhesion followed by trans-endothelial migration. Once within the vessel wall,
monocytes differentiate into tissue macrophages which internalise oxidised LDL eventually
becoming foam cells. This differentiation process is accelerated by bacterial
lipopolysaccharide (LPS).
In this study we look at the transcriptional changes that occur during monocyte activation in
response to two distinct stimuli – infection caused by the presence of LPS and exposure to
adhesion molecules, specifically P-selectin which is expressed by both activated endothelial
cells and platelets. Comparisons of the transcription profiles of activated monocytes have
identified a number of differentially regulated genes. Three distinct groups can be identified
– infection responsive genes, inflammation responsive genes and genes that respond to both
stimuli. A selection of these genes is currently being validated and will be investigated
further to identify their role in monocyte function and how it may be relevant in the setting
of atherosclerosis.
Inter-individual variation in the innate immune response to LPS was also explored in 208
individuals. Our results show that there is a 10-fold range of response to LPS and that in the
short-term, this variation is reproducible. Comparison of transcription profiles of individuals
who show the highest and lowest responses can identify genes involved in magnitude of
response, which might be an important factor in the progression of atherosclerosis.