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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.70169 |
| Date | January 1991 |
| Creators | Descoteaux, Albert |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Institute of Parasitology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001222309, proquestno: AAINN67526, Theses scanned by UMI/ProQuest. |
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