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Study on the effect of Leishmania donovani infection on signal transduction in macrophages

The ability of tumor necrosis factor (TNF) and lipopolysaccharide (LPS) to stimulate gene expression in bone marrow-derived macrophages (BMM) was first compared. It is demonstrated that they stimulated gene expression through distinct signal transduction pathways and that TNF stimulated gene expression through a protein kinase C (PKC)-dependent signal transduction pathway. The effect of the intracellular parasite of macrophages Leishmania donovani in BMM was then investigated. It is demonstrated that L. donovani impaired c-fos and TNF gene expression through two distinct mechanisms. The first one is indomethacin-reversible, and the second one involves the inhibition of diacylglycerol-induced PKC-dependent gene expression. A purified cell surface glycoconjugate of the parasite, termed lipophosphoglycan, selectively inhibited PKC-dependent gene expression in BMM. While the translocation of PKC from the cytosol to the membrane was normal, total cellular PKC enzyme activity was inhibited in the U937 human monocyte cell line pretreated with lipophosphoglycan.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.70169
Date January 1991
CreatorsDescoteaux, Albert
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageDoctor of Philosophy (Institute of Parasitology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001222309, proquestno: AAINN67526, Theses scanned by UMI/ProQuest.

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