The Effect of Lipids on Neutrophil-Derived Microparticle formation
Dr Victoria Ridger, Dr Amanda Burnett and Prof Paul Hellewell
Microparticles were first described by Wolf et al in 1967 as “platelet dust” [1]. Since then many different
cell types have been found to release these membrane bound vesicles in response to various stimuli.
The phenotype (size, content, membrane expression, annexin V expression) of microparticles varies
according to the cell source and stimulus [2]. The role of neutrophil-derived microparticles in
atherogenesis has, as yet, not been investigated; it is possible that these cell-derived entities play a
significant role in propagating and exacerbating the inflammatory components of the atherogenic
process. We have recently shown that treating peripheral blood neutrophils with L-NAME resulted in the
production of microparticles [3]. These microparticles were found to express the adhesion molecules
PSGL-1 and L-selectin on their surface and increased transendothelial migration of neutrophils in vitro.
The release of microparticles may therefore provide a mechanism by which local concentrations of
inflammatory mediators can be amplified, exacerbating leukocyte adhesion and transendothelial
migration in diseases such as atherosclerosis. Low density lipoprotein (LDL), often referred to as bad
cholesterol, is strongly implicated in the development of atherosclerosis and our preliminary data show
that neutrophils are able to respond to LDL and modified LDL by producing microparticles with different
characteristics. This studentship will investigate the effect of LDL or modified LDL on neutrophil
microparticle phenotype and function, and determine the mechanisms by which these effects occur.
1.
2.
3.
Wolf, P., The nature and significance of platelet products in human plasma. Br J Haematol, 1967.
13(3): p. 269-88.
VanWijk, M.J., et al., Microparticles in cardiovascular diseases. Cardiovasc Res, 2003. 59(2): p.
277-87.
Nolan, S., et al., Nitric oxide regulates neutrophil migration through microparticle formation. Am
J Pathol, 2008. 172(1): p. 265-73.
Informal enquiries can be directed to Dr Victoria Ridger (v.c.ridger@sheffield.ac.uk).
This project is in competition for MRC funding.