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| Identifier |
000381087 |
| Title |
Διερεύνηση του ρόλου της έκφρασης των μορίων FAS/FASL και CD40/CD40L στις μυελικές κοκκιοκυτταρικές προβαθμίδες,και μελέτη των μηχανισμών ομοιόστασης της κοκκιοποίησης |
| Alternative Title |
Investigation of the role of fasifasligand and CD40/CD40L molecules expression on bone marrow granulopoietic progenitors and precursor cells and study of the homeostatic mechanisms of granulopoiesis |
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Author
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Μαυρουδή, Ειρήνη
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Thesis advisor
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Παπαδάκη, Ελένη
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Reviewer
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Ηλιόπουλος, Αριστείδης
Τσατσάνης, Χρήστος
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| Abstract |
Background: CD40 is a member of tumor necrosis factor (TNF) receptor family and upon interaction with its cognate ligand (CD40L) it induces diverse biologic responses related to cell survival/growth. Because altered CD40/CD40L interactions have been associated with neutropenia, we investigated the role of CD40/CD40L on human granulopoiesis.
Design-Methods: CD40 expression was assessed on immunomagnetically sorted CD34+, CD34-/CD33+ and CD34-/CD33-/CD15+ normal bone marrow (BM) cells, whch represent sequential stages of the granulocytic development. We evaluated the proportion of apoptotic cells in the above cell populations following CD40 activation. We also investigated the effect of CD40L on the production of granulopoiesis-promoting cytokines by stromal layers of long-term BM cultures that mimic the BM microenvironment.
Results: CD40 and CD40L were minimally expressed on CD34+, CD34-/CD33+, CD34-/CD33-/CD15+ cells but CD40 was substantially induced in the presence of TNFα. Cross-linking of CD40 in the above cell populations resulted in induction of apoptosis that was further enhanced in the presence of FasL. CD40 activation in primary cells resulted in Fas up-regulation, providing a possible mechanism for the CD40-mediated apoptotic effect. Addition of CD40L in clonogenic assays resulted in significant decrease in the colony-forming capacity of BM mononuclear cells from patients with chronic neutropenia, presumably expressing high levels of CD40 in the progenitor cells, and this effect was reversed upon CD40 blockade. CD40 was constitutively expressed on long-term BM culture stromal cells and upon activation resulted in an increase in granulocyte-colony stimulating factor and granulocyte/macrophage-colony stimulating factor production.
Conclusions: These data show that CD40/CD40L interactions may promote granulopoiesis under steady state conditions by inducing the stromal release of granulopoiesis-supporting cytokines whereas under inflammatory conditions they may affect the granulocytic progenitor/precursor cell survival by accelerating the Fas-mediated apoptosis.
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| Language |
Greek |
| Subject |
CD40 |
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CD40L |
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Chronic idiopathic neutropenia |
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FAS |
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Granulopoiesis |
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Hematopoiesis |
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Κοκκιοποίηση |
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Χρόνια ιδιοπαθής ουδετεροπενία |
| Issue date |
2011-12-15 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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| Views |
266 |
Διερεύνηση του ρόλου της έκφρασης των μορίων FAS/FASL και CD40/CD40L στις μυελικές κοκκιοκυτταρικές προβαθμίδες,και μελέτη των μηχανισμών ομοιόστασης της κοκκιοποίησης
