Chemical inhibition of Fcgamma-receptor-mediated phagocytosis.
Published: 2006
Language: eng
Number of pages: 139
ISBN-13: 9780494212509
Description: Immune thrombocytopenic purpura is characterized by FcgammaR-mediated phagocytosis of autoantibody sensitized platelets by the MPS. These are many disadvantages to immunoglobulin IVIg and anti-RhD therapies and alternatives are needed. Certain chemicals reportedly inhibit FcgammaR-mediated phagocytosis  in vitro. We attempt to characterize structural requirements for inhibition, enhance efficacy of immunoglobulin with candidate compounds and evaluate efficacy of candidates in vivo. Efficacy of treatments  in vitro was assessed using a monocyte monolayer assay (MMA). For chemically-treated immunoglobulin, immunoglobulin and thimerosal were mixed, dialysed and evaluated in the MMA compared to controls. A murine model of ITP was also used. We report that of the chemicals tested, thiol reactivity and a p-nitrophenyl group were required for optimal inhibition. Treating anti-RhD with thimerosal enhanced the efficacy of anti-RhD by approximately 100%. We also show that thimerosal and p-nitrophenylethanol have efficacy  in vivo. These findings may lead to the replacement or enhancement of immunoglobulin therapy.
Notes: Source: Masters Abstracts International, Volume: 45-03, page: 1449.

Thesis (M.Sc.)--University of Toronto, 2006.

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