LE3 .A278 2008

2008

Smith, Todd

Acadia University

Bachelor of Science

Honours

Biology

Biology

Plasmodium falciparum, the protozoan parasite that causes the most lethal form of human malaria, is responsible for the death of more than two million people each year. One aspect of innate immunity against this parasite is the antibody-independent phagocytosis of P. falciparum-infected erythrocytes (PEs) by monocytes and macrophages. A previous study in our laboratory revealed significant variability in the efficiency of phagocytosis of four genetically different clones of PEs by macrophages. The objective of this project was to assess the roles of different membrane receptors potentially involved in adherence and phagocytosis of four clones of PEs by macrophages in order to determine if the previously observed variation in phagocytosis of different clones is related to the receptors that are recognized by each clone. Membrane receptors (CD36, ICAM-1, CD14, CD45, MBR) of macrophages from three human volunteers were blocked with monoclonal antibodies, incubated with PEs for 4 hr in a phagocytosis assay, and examined on stained cover slips and in live assays. Macrophages blocked with anti- CD36 had a significantly lower phagocytic efficiency of all four clones when compared with normalized controls. However, blocking with anti-CD36 decreased the phagocytic efficiency of ITG-2F6 to a significantly greater degree than the other clones. Also, clone ITG-2F6 was taken up with a significantly lower efficiency when blocked with anti- MBR. Live microscopy showed that clone ITG-2F6 adhered to macrophages to a significantly higher degree than did clone 3D7A. These results indicate that genetically different clones of parasites adhere to macrophages via different membrane receptors with differential affinity, and suggest that variation in parasite ligands on the surface of infected erythrocytes mediate adherence and subsequent phagocytosis.

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https://scholar.acadiau.ca/islandora/object/theses:539