Expression Of Integrin Markers On Anti- Malaria Effector Cells In The Placenta Of Post Partum Women In Western Kenya.

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 anti-malarial 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.