Effect of exposure to malaria parasites on IGFBP7 expression profile of endothelial cells

Abstract

The pathogenesis of severe malaria revolves around the pathological changes within the vasculature during the infection. Infected erythrocytes (IRBC) can sequester within the microvasculature via phenomena such as IRBC-endothelial cytoadherence, rosetting, and platelet mediated agglutination of IRBC. This results in hampering of blood flow, giving rise to endothelial activation and injuries. Recently, insulin-like growth factor binding protein-7 (IGFBP7) has been reported to stimulate rosette formation of IRBC. As IGFBP7 has been associated with several vascular disorders, we decided to quantitate the IGFBP7 secretion by endothelial cells upon exposure to the parasite antigens so as to understand the microvasculature dynamics during malaria pathogenesis. We used human endothelial cell lines derived from microvasculature of brain, lungs and kidneys. The endothelial cells were exposed to culture supernatant of parasites Plasmodium falciparum (strain 3D7) and P. knowlesi (strain A1-H.1) separately for 24 hours prior to IGFBP7 quantification via ELISA performed on culture supernatant of the endothelial cells. We found that only the kidney-derived human renal glomerular endothelial cells (HGREC) that were exposed to P. knowlesi culture supernatant demonstrated significant increment in IGFBP7 secretion. This study shows that different endothelial cells react differently to different species of malaria parasites in the context of IGFBP7 secretion.