Expression of integrin markers on anti- malaria effector cells in the placenta of post partum women in Western Kenya
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Date
2017-06
Authors
Mwalimu, Stephen M.
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Abstract
Malaria in pregnancy has been linked to utero-placental vascular insufficiency and fetal fatalities.
The immunity to placental malaria may be mediated in part by monocytes and T cells that
accumulate in the placenta intervillous space. The immunological basis for retention of antimalarial
effector cells in the intervillous space and the role of leucocyte integrins in the intervillous
space is not well understood. Leucocytes use surface receptors to mediate binding on endothelial
villous walls. Among these receptors, integrins play a crucial role in leucocytes tethering and
extravasation. The surface expression of integrins and intracellular adhesion molecule-1(ICAM-
1) on T cells and monocytes in reduced incidence of placental malaria in multigravidae has not
been studied. The objective of this study was to analyse the integrins and compare their expression
patterns on peripheral and placental T cells and monocytes. Placental and peripheral leucocytes
were processed from whole blood peripheral and intervillous blood. The washed leucocytes were
stained with specific monoclonal antibodies and analysed by flow cytometry for ICAM-1, very
late leucocyte antigen-4 (VLA), leucocyte function associated antigen-1(LFA-1) and macrophage
antigen-1 (MaC-1). Microscopy was used to determine peripheral and placental malaria infections,
while parasites density was calculated from the number of malaria parasites per 300 leucocytes
and converted into parasites per microliter of blood. Statistical analysis was done using Graph Pad
Prism version 5.0. Differences in the expression of integrins between two groups and within cell
population were performed by students paired t-test. Statistical significance was considered for
probability values less than 0 .05 (˂ 0.05).The results indicated the expression pattern of most
integrins studied was altered in placental blood in presence of malaria parasites. In placental
malaria ICAM-1 and VLA-4, MaC-1 and LFA-1 expression in placental monocytes was
significantly up regulated (p < 0.0001). Surface expression of ICAM-1, VLA-4 and LFA-1 was
significant high on peripheral T cells (P < 0.0001) in presence malaria parasites except for MaC-
1. Gravidity and parasite density in the intervillous and peripheral blood did not seem to affect the
expression pattern of these integrins and ICAM-1. The results from this study suggest that
leucocyte integrins activation in the placental blood is inducible by accumulation of infected red
blood cells in the intervillous blood. However, the expression pattern is different on peripheral and
intervillous T cells and monocytes. The study also demonstrated parasite density and gravidity
does not affect the expression patterns of leucocyte integrins and ICAM -1 on peripheral and
placental T cells and monocytes. Therefore to develop anti-adhesion vaccines and therapeutics to
reduce malaria in pregnancy there is need to understand the role of leucocyte integrins in the
pathogenesis placental malaria.
Description
Research thesis submitted in partial fulfilment of the requirements for the award of Masters Science Degree
(Infectious Diseases- Immunology) in the School of Medicine, Kenyatta University. June, 2017