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Identifier

000364575

Title

Μελέτη των μορίων CD40 και CD154 στα προγονικά αιμοποιητικά κύτταρα και τα κύτταρα του αιμοποιητικού μικροπεριβάλλοντιος πασχόντων απο σύνδρομα μυελικής ανεπάρκειας

Alternative Title

Study of CD40 and CD154 in haemopoietic stem cells and bone marrow microenviromeny of patients with bone marrow failure syndromes.

Author

Πυροβολάκη, Αικατερίνη

Thesis advisor

Παπαδάκη, Ελένη

Reviewer

Ηλιόπουλος, Γεώργιο
Ηλιόπουλος, Αριστείδη
Μπούμπασ, Δημήτριος
Σιδηρόπουλος, Πρόδρομος
Γουλιέλμος, Γεώργιος
Σουρβίνος, Γεώργιος

Abstract

Patients with systemic lupus erythematosus (SLE) display increased apoptosis of bone marrow (BM) CD34+ hematopoietic progenitor cells. This study was undertaken to evaluate the expression of CD40 and CD40L in the BM of SLE patients, and to explore the possible involvement of these molecules in apoptosis of CD34+ cells. Methods. The proportion and survival characteristics of CD40+ cells within the BM CD34+ fraction from SLE patients and healthy controls were evaluated by flow cytometry. The production of CD40L by BM stromal cells was assessed using longterm BM cultures and the effect of CD40L on the survival characteristics and clonogenic potential of CD34+ cells was evaluated ex vivo by flow cytometry and clonogenic assays. Results. SLE patients displayed an increased proportion of CD40+ cells within the CD34+ fraction as compared with controls. The CD34+CD40+ subpopulation contained an increased proportion of apoptotic cells compared with the CD34+CD40‐ fraction in patients and controls, suggesting that CD40 is involved in the apoptosis of CD34+ cells. Stimulation of patients’ CD34+ cells with CD40L increased the proportion of apoptotic cells and decreased the proportion of colony-forming cells as compared with untreated cultures. The CD40L-mediated effects were amplified following treatment with recombinant Fas ligand, suggesting that the effects of these ligands are synergistic. CD40L levels were significantly increased in long-term BM culture supernatants and adherent layers of BM cells from SLE patients as compared with controls. Conclusion. These data reveal a novel role for the CD40/CD40L dyad in SLE by demonstrating that upregulation and induction of CD40 on BM CD34+ cells from patients with SLE contribute to the amplification of Fas-mediated apoptosis of progenitor cells.

Language

Greek

Subject

Bone marrow failure syndromes

CD154

CD40

Hemic and Lymphatic systems

Αίμα και λεμφικό σύστημα

Σύνδρομα μυελικής ανεπάρκειας

Issue date

2009-12-14

Collection