Infiltrated macrophages contribute to recovery after ischemic injury but not to ischemic preconditioning in kidneys

BACKGROUND: Macrophages are associated with ischemia/reperfusion (I/R) injury; however, the role of macrophages that have infiltrated into tissues remains unclear. Therefore, we investigated whether infiltrated macrophages influence recovery after kidney I/R injury and affect the phenomenon of ischemic preconditioning, in which previous ischemia affords the kidney resistance to subsequent ischemia. METHODS: Mice were subjected to 30 min of bilateral renal ischemia on day 0, then intravenously administered either liposome-encapsulated dichloromethylene bisphosphonate (Cl2MBP; Lipo-clodronate, a remover of tissue macrophages) or PBS (Lipo-PBS) on day 6 and were then subjected to an additional 30 min of bilateral renal ischemia on day 8. RESULTS: Administration of lipoclodronate removed the infiltrated macrophages after I/R. The number of apoptotic and necrotic cells, as well as superoxide and peroxynitrite levels in kidneys from mice that received Lipo-clodronate, was significantly greater than those in kidneys from mice that were administered Lipo-PBS. Proliferating cell nuclear antigen (PCNA) expression was greater in kidneys from mice that were treated with Lipo-clodronate than in those from mice treated with Lipo-PBS. Thirty min of ischemic preconditioning protected the kidneys from 30 min of ischemia induced 8 days later. There was no difference in the plasma creatinine levels of mice treated with Lipo-clodronate or Lipo-PBS. CONCLUSIONS: Our results demonstrated that the infiltrated macrophages removed dead and dying cells and accelerated recovery after ischemia/reperfusion injury but did not make a critical contribution to ischemic preconditioning.