Item – Theses Canada

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OCLC number
1335712470
Link(s) to full text
LAC copy
Author
Mills, Caroline Dawn.
Title
Characterization of ligands mediating adherence of Plasmodium falciparum-infected erythrocytes to CD36 and ICAM-1.
Degree
M.Sc. -- University of Toronto, 1999.
Publisher
[Toronto, Ontario] : University of Toronto, 1999
Description
1 online resource
Abstract
All models of cerebral malaria pathogenesis involve sequestration; the unique ability of 'Plasmodium falciparum' IE to bind to vascular endothelium. Thus central to understanding cerebral malaria is the elucidation of the molecular interactions of sequestration. In these studies, detailed time course experiments were performed to help define the roles of the ligands PfEMP1neoantigens and band 3 neoantigens and receptors CD36 and ICAM-1. The ability to bind to CD36 and ICAM-1 is an off/on event closely linked to the ring to trophozoite transition. Band 3 neoantigens IF4,3H3 we surface expressed beginning at 12 hours and IC4 is present on the surface coincident with the onset of binding. These neoantigens are coincidentally present on individual BE, with unique patterns of distribution. PfEMP1 is present on the surface of fixed and live infected erythrocytes coincident with the onset of binding. Confocal microscopy revealed that the protein is synthesized beginning 8 hours before binding in the parasite cytoplasm. In agreement with this, is the upregulation of 'var' gene transcription in the late ring stage demonstrated by RT-PCR. Dual labeling studies demonstrate that the two temporally relevant ligands, PfEMP1 and 1C4, are both found on single IEs, but appear to have distinct distributions, suggesting that they may function independently in promoting IE sequestration.
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hdl.handle.net
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tspace.library.utoronto.ca