title: Mannan-binding lectin recognizes structures on ischaemic reperfused mouse kidneys and is implicated in tissue injury.
abstract: Organ damage as a consequence of ischaemia and reperfusion (I/R) is a major clinical problem in an acute renal failure and transplantation. Ligands on surfaces of endothelial cells that are exposed due to the ischaemia may be recognized by pattern recognition molecules such as mannan-binding lectin (MBL), inducing complement activation. We examined the contribution of the MBL complement pathway in a bilateral renal I/R model (45 min of ischaemia followed by 24 h of reperfusion), using transgenic mice deficient in MBL-A and MBL-C [MBL double knockout (MBL DKO)] and in wildtype (WT) mice. Kidney damages, which were evaluated by levels of blood urea nitrogen (BUN) and creatinine, showed that MBL DKO mice were significantly protected compared with WT mice. MBL DKO mice, reconstituted with recombinant human MBL, showed a dose-dependent severity of kidney injury increasing to a comparable level to WT mice. Acute tubular necrosis was evident in WT mice but not in MBL DKO mice after I/R, confirming renal damages in WT mice. MBL ligands in kidneys were observed to be present after I/R but not in sham-operated mice. C3a (desArg) levels in MBL DKO mice were decreased after I/R compared with that in WT mice, indicating less complement activation that was correlated with less C3 deposition in the kidneys of MBL DKO mice. Our data implicate a role of MBL in I/R-induced kidney injury.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Aarhus, Denmark. mmk@microbiology.au.dk
authors.forename: M
authors.initials: M
authors.lastname: Møller-Kristensen
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Ruseva
authors.forename: S
authors.initials: S
authors.lastname: Thiel
authors.forename: S
authors.initials: S
authors.lastname: Nielsen
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: L
authors.initials: L
authors.lastname: Shi
authors.forename: A
authors.initials: A
authors.lastname: Ezekowitz
authors.forename: J C
authors.initials: JC
authors.lastname: Jensenius
authors.forename: M
authors.initials: M
authors.lastname: Gadjeva
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology* / Q000473:pathology; D000818:Animals; D015926:Complement C3a / Q000031:analogs & derivatives* / Q000032:analysis; D037582:Complement Pathway, Mannose-Binding Lectin; D004195:Disease Models, Animal; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009336:Necrosis / Q000473:pathology; D015427:Reperfusion Injury / Q000473:pathology
chemical_list: D037601:Mannose-Binding Lectin; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a