Macrophages contribute to the initiation of ischaemic acute renal failure in rats

  • Jo S
  • Sung S
  • Cho W
 et al. 
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Abstract

BACKGROUND: Although neutrophils and T cells are important in mediating renal injury following ischaemia/reperfusion, the role of macrophages is still unknown. Using liposomal clodronate (LC), we investigated the effect of systemic monocyte-macrophage depletion on renal damage in ischaemic acute renal failure in rats. METHODS: Male Sprague-Dawley rats were injected by LC or liposomal vehicle and underwent bilateral renal pedicle clamping (40 min) or sham ischaemia. Biochemical and histological renal damage was assessed and gene expression kinetics of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and monocyte chemoattractant protein-1 (MCP-1) using quantitative real-time reverse transcription-polymerase chain reaction were conducted at 4, 24 and 72 h after reperfusion. RESULTS: The percentage of peripheral blood monocytes and ectodysplasin-1-positive cells in liver decreased significantly in LC-treated animals at 24 h. Systemic monocyte-macrophage depletion resulted in (a) less severe tubular necrosis, (b) reduced inflammation and (c) reduced apoptosis of renal tubular epithelial cells. Gene expression kinetics showed that IL-6 gene expression peaked early at 4 h after reperfusion, followed by TNF-alpha, IL-1beta and MCP-1 expressions, which peaked at 24 h. Systemic monocyte-macrophage depletion significantly reduced these cytokine and chemokine gene expressions. CONCLUSIONS: These results suggest that macrophages are an important mediator in the initiation period of ischaemia/reperfusion injury and strategies that limit initial macrophage infiltration or activation can be useful in the treatment of acute renal failure.

Author-supplied keywords

  • Apoptosis
  • Cytokine/chemokine
  • Inflammation
  • Ischaemia/reperfusion
  • Liposomal clodronate
  • Macrophages

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Authors

  • Sang Kyung Jo

  • Su Ah Sung

  • Won Yong Cho

  • Kang Jee Go

  • Hyoung Kyu Kim

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