The mannose-binding lectin-pathway is involved in complement activation in the course of renal ischemia-reperfusion injury

Am J Pathol. 2004 Nov;165(5):1677-88. doi: 10.1016/S0002-9440(10)63424-4.


Ischemia-reperfusion (I/R) is an important cause of acute renal failure (ARF). The complement system appears to be essentially involved in I/R injury. However, via which pathway the complement system is activated and in particular whether the mannose-binding lectin (MBL)-pathway is activated is unclear. This tempted us to study the activation and regulation of the MBL-pathway in the course of experimental renal I/R injury and in clinical post-transplant ARF. Mice subjected to renal I/R displayed evident renal MBL-depositions, depending on the duration of warm ischemia, in the early reperfusion phase. Renal deposition of C3, C6 and C9 was observed in the later reperfusion phase. The deposition of MBL-A and -C completely co-localized with the late complement factor C6, showing that MBL is involved in complement activation in the course of renal I/R injury. Moreover, the degree of early MBL-deposition correlated with complement activation, neutrophil-influx, and organ-failure observed in the later reperfusion phase. In serum of mice subjected to renal I/R MBL-A, levels increased in contrast to MBL-C levels, which dropped evidently. In line, liver mRNA levels for MBL-A increased, whereas MBL-C levels decreased. Renal MBL mRNA levels rapidly dropped in the course of renal I/R. Finally, in human biopsies, MBL-depositions were observed early after transplantation of ischemically injured kidneys. In line with our experimental data, in ischemically injured grafts displaying post-transplant organ-failure extensive MBL depositions were observed in peritubular capillaries and tubular epithelial cells. In conclusion, in experimental renal I/R injury and clinical post-transplant ARF the MBL-pathway is activated, followed by activation of the complement system. These data indicate that the MBL-pathway is involved in ischemia-induced complement activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Biopsy
  • Complement Activation
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunohistochemistry
  • Kidney / metabolism
  • Kidney / pathology*
  • Lectins
  • Liver / metabolism
  • Lung / metabolism
  • Male
  • Mannose / chemistry*
  • Mannose-Binding Lectin / chemistry*
  • Mice
  • Neutrophils / metabolism
  • Peroxidase / metabolism
  • Protein Binding
  • RNA, Messenger / metabolism
  • Reperfusion Injury / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors


  • Antibodies, Monoclonal
  • Lectins
  • Mannose-Binding Lectin
  • RNA, Messenger
  • Peroxidase
  • Mannose