The mannose-binding lectin-pathway is involved in complement activation in the course of renal ischemia-reperfusion injury.
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.
de Vries
Bart
B
Department of General Surgery, Maastricht University, P.O. Box 616, Universiteitssingel 50, 6200 MD Maastricht, the Netherlands.
Walter
Sarah J
SJ
Peutz-Kootstra
Carine J
CJ
Wolfs
Tim G A M
TG
van Heurn
L W Ernest
LW
Buurman
Wim A
WA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001706:Biopsy; D003167:Complement Activation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D037102:Lectins; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008358:Mannose / Q000737:chemistry*; D037601:Mannose-Binding Lectin / Q000737:chemistry*; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000911:Antibodies, Monoclonal; D037102:Lectins; D037601:Mannose-Binding Lectin; D012333:RNA, Messenger; D009195:Peroxidase; D008358:Mannose