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.
Jang
Hee-Seong
HS
Department of Anatomy and BK21 Project, Kyungpook National University School of Medicine, Junggu, Daegu, Korea.
Kim
Jinu
J
Park
Yong-Ki
YK
Park
Kwon Moo
KM
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species