Item – Theses Canada

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OCLC number
77378523
Link(s) to full text
LAC copy
LAC copy
Author
Yipp, Bryan,1975-
Title
Molecular mechanisms of the CD36-Plasmodium falciparum interaction in cytoadherence.
Degree
M. Sc. -- University of Calgary, 2005
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2006]
Description
2 microfiches
Notes
Includes bibliographical references.
Abstract
The central pathological process in severe 'P. falciparum' malaria is the cytoadherence of infected erythrocytes (IRBC) to microvascular endothelial receptors including CD36, ICAM-1, VCAM-1 and P-selectin. The molecular mechanisms of IRBC firm adhesion to CD36 are incompletely understood, particularily in vivo. Using a human/SCID mouse chimeric model of cytoadherence, we found that P-selectin and ICAM-1 enhance firm adhesion to CD36 through rolling-increased and decreased mechanisms. As well, a recombinant peptide (y179) based on the parasite protein PfEMP1 was found to inhibit and reverse firm adhesion of multiple clinical parasite isolates in vitro and in vivo. Finally, a novel model of firm adhesion involving both outside-in and inside-out signaling mechansims was demonstrated. The PfEMP1-CD36 interaction induced a Src-family kinase signal (outside-in) that is linked to an ecto-alkaline phosphatase capable of enhancing subsequent firm adhesion (inside-out). Optimal firm adhesion is dependent on both Src-family kinase activation and ecto-alkaline phosphatase activity.
ISBN
0494038403
9780494038406