Projects per year
The role of resident renal mononuclear phagocytes in acute kidney injury is controversial with experimental data suggesting both deleterious and protective functions. To help resolve this, we used mice transgenic for the human diphtheria toxin receptor under the control of the CD11b promoter and treated them with diphtheria toxin, or liposomal clodronate, or both to deplete monocyte/mononuclear phagocytes prior to renal ischemia/reperfusion injury. Although either system effectively depleted circulating monocytes and resident mononuclear phagocytes, depletion was most marked in diphtheria toxin-treated mice. Despite this, diphtheria toxin treatment did not protect from renal ischemia. In contrast, mice treated with clodronate exhibited reduced renal failure and acute tubular necrosis, suggesting key differences between these depletion strategies. Clodronate did not deplete CD206-positive renal macrophages and, unlike diphtheria toxin, left resident CD11c-positive cells unscathed while inducing dramatic apoptosis in hepatic and splenic mononuclear phagocyte populations. Abolition of the protected phenotype by administration of diphtheria toxin to clodronate-treated mice suggested that the protective effect of clodronate resulted from the presence of a cytoprotective intrarenal population of mononuclear phagocytes sensitive to diphtheria toxin-mediated ablation.
|Number of pages||6|
|Publication status||Published - Oct 2012|
- ISCHEMIA-REPERFUSION INJURY
- ACUTE KIDNEY INJURY
- acute kidney injury
- RESIDENT DENDRITIC CELLS
- cell ablation
- MONOCYTE LINEAGE
FingerprintDive into the research topics of 'Macrophage/monocyte depletion by clodronate, but not diphtheria toxin, improves renal ischemia/reperfusion injury in mice'. Together they form a unique fingerprint.
- 2 Finished
PhD STUDENT - JOANNE SIMPSON - Supervisor MOHINI GRAY
1/09/12 → 31/08/16
recovery from Ischaemia-Reperfusion Injury After Renal Transplantation
Prost, S., Bellamy, C., Dunbar, D. & Kluth, D.
UK central government bodies/local authorities, health and hospital authorities
1/09/12 → 31/08/15