Binding of mannose-binding lectin to fructosamines: a potential link between hyperglycaemia and complement activation in diabetes

Diabetes Metab Res Rev. 2010 May;26(4):254-60. doi: 10.1002/dmrr.1079.


Background: Complement activation via the MBL pathway has been proposed to play a role in the pathogenesis of diabetic complications. As protein glycation is increased in diabetes, we tested the possibility that the glycation product fructoselysine is a ligand for MBL and that its interaction with this protein may initiate complement activation.

Methods: We investigated the binding of MBL to fructoselysine by chromatography of human serum on fructoselysine-Sepharose, followed by Western blot and mass spectrometry analysis. We also performed enzyme-linked immunosorbent assays using purified MBL and fructoselysine-derivatized (binding assay) or mannan-coated plates (inhibition assay). Complement activation was determined by the fixation of C3d following incubation of fructoselysine-derivatized plates with serum from subjects with different levels of MBL.

Results: MBL and its associated proteases were selectively purified from serum by chromatography on fructoselysine-Sepharose. Competition experiments indicated that MBL had a similar affinity for mannose, fructose and fructoselysine. MBL bound, in a highly cooperative manner, to fructoselysine-derivatized plates. This binding was associated with complement activation and was much lower with serum from subjects with low-MBL genotypes.

Conclusions: MBL binding to fructoselysine and the ensuing complement activation may provide a physiopathological link between enhanced glycation and complement activation in diabetes. The cooperative character of this binding may explain the high sensitivity of diabetic complications to hyperglycaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Chromatography, Affinity
  • Complement Activation*
  • Diabetes Mellitus, Type 2 / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Lysine / analogs & derivatives*
  • Lysine / metabolism
  • Mannose-Binding Lectin / blood
  • Mannose-Binding Lectin / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor)


  • Blood Glucose
  • Mannose-Binding Lectin
  • fructosyl-lysine
  • Phosphotransferases (Alcohol Group Acceptor)
  • fructosamine-3-kinase
  • Lysine