Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.653453
Title: Inflammatory macrophages and renal tubular epithelial cell apoptosis
Author: Kipari, T. M. J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Abstract:
Macrophages play a key role in renal inflammation and may be cytotoxic to resident cells within tissues. I begin this thesis by examining the effect of macrophages upon the level of apoptosis and proliferation in tubular epithelial cells in vitro. I then went on to examine the role of NO in vivo in the murine model of unilateral ureteric obstruction (UUO) characterised by tubular cell apoptosis and interstitial fibrosis. The specific iNOS inhibitor L-NIL (control D-NIL) was administered between days 5 to 7 following UUO. Mice were sacrificed at day 7 and the obstructed kidney removed for histological analysis. L-NIL treatment did not affect macrophage infiltration but did reduce both tubular and interstitial cell apoptosis. Proliferation of tubular cells and interstitial cells was unaffected. Interstitial fibrosis was significantly increased by L-NIL treatment. I also investigated the effect of conditional macrophage ablation in the UUO model. The conditional macrophage ablation mice used in these studies are transgenic for the human diphtheria toxin receptor (DTR) under the CD11b promoter (CD11b-DTR mice). Intraperitoneal (IP) administration of diphtheria toxin (DT) to DTR mice results in the rapid and specific depletion of monocytes and macrophages. DTR mice underwent UUO at day 0 and either DT or PBS was administered IP on days 5, 6 and 7. Mice were sacrificed at day 7 and the obstructed kidney removed for histological analysis. Administration of DT resulted in a 3-fold reduction in interstitial macrophage accumulation in obstructed kidneys. However, macrophage depletion had no effect upon proximal or distal tubular cell proliferation or apoptosis. Interestingly, macrophage depletion had no effect upon the accumulation of myofibroblasts but attenuated interstitial fibrosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.653453  DOI: Not available
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