Tropism of endothelial cytoadhesion by plasmodium falciparum-IRBCs

• Main Author: Li, Yihuan
• Other Authors: Lee Wenn Chyau
• Format: Final Year Project
• Language: English
• Published: 2019
• Subjects: Science::Biological sciences
• Online Access: http://hdl.handle.net/10356/78853
• Institution: Nanyang Technological University

Ligands expressed on Plasmodium falciparum-IRBC surface (e.g. PfEMP1, STEVOR and RIFIN etc) bind to different receptors on microvasculature endothelial cells as well as rosette with uninfected erythrocytes. These events give rise to IRBC sequestration, which is associated to malaria pathogenesis. The direct interaction between IRBC and EPCR can activate endothelial cells. However, it is unclear whether endothelial cells can be activated without such direct contact-based interactions. Hence, tropism of P. falciparum endothelial cytoadhesion and effect of soluble parasite-derived antigens on IRBC cytoadhesion were investigated. Laboratory-adapted parasite isolates were used to test the IRBC cytoadherence and rosetting rates with endothelial cells derived from three different organs (brain, lungs and kidney). These rates were then compared between endothelial cells in naïve settings and primed settings (prior exposure to soluble parasite-derived antigens). Recombinant human EPCR were used to investigate the essentiality of EPCR in endothelial cell activation independent of IRBC-endothelial contact. Endothelial cytoadherence and rosetting rates increased for most parasite isolates in primed settings. Competitive inhibition of EPCR had insignificant effect on endothelial cytoadherence rate. These suggests that soluble parasite-derived antigens can activate endothelial cells without direct IRBC-EPCR interaction. Besides, tropism of endothelial cytoadhesion varied among parasites of different geographical origins.