title: Role of interaction of mannan-binding protein with meprins at the initial step of complement activation in ischemia/reperfusion injury to mouse kidney.
abstract: Ischemia/reperfusion (I/R) is an important cause of acute renal failure. Recent studies have shown that the complement system mediated by the mannan-binding protein (MBP), which is a C-type serum lectin recognizing mannose, fucose and N-acetylglucosamine residues, plays a critical role in the pathogenesis of ischemic acute renal failure. MBP causes complement activation through the MBP lectin pathway and a resulting complement component, C3b, is accumulated on the brush borders of kidney proximal tubules in a renal I/R-operated mouse kidney. However, the initial step of the complement activation has not been studied extensively. We previously identified both meprins α and β, highly glycosylated zinc metalloproteases, localized on kidney proximal tubules as endogenous MBP ligands. In the present study, we demonstrated that serum-type MBP (S-MBP) and C3b were co-localized with meprins on both the cortex and the medulla in the renal I/R-operated mouse kidney. S-MBP was indicated to interact with meprins in vivo in the I/R-operated mouse kidney and was shown to initiate the complement activation through the interaction with meprins in vitro. Taken together, the present study strongly suggested that the binding of S-MBP to meprins triggers the complement activation through the lectin pathway and may cause the acute renal failure due to I/R on kidney transplantation and hemorrhagic shock.
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirano
authors.forename: Bruce Y
authors.initials: BY
authors.lastname: Ma
authors.forename: Nobuko
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Shogo
authors.initials: S
authors.lastname: Oka
authors.forename: Toshisuke
authors.initials: T
authors.lastname: Kawasaki
mesh_terms: D000818:Animals; D003179:Complement C3b / Q000378:metabolism; D037582:Complement Pathway, Mannose-Binding Lectin; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D011485:Protein Binding; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D037601:Mannose-Binding Lectin; D003179:Complement C3b; D008666:Metalloendopeptidases; C053833:meprin A; C095663:meprin B