S-nitrosylation of mannose binding lectin regulates its functional activities and the formation of autoantibody in rheumatoid arthritis

Nitric Oxide. 2008 Jun;18(4):266-73. doi: 10.1016/j.niox.2008.01.009. Epub 2008 Feb 29.

Abstract

The possibility of post-translational modifications of mannose binding lectin (MBL) leading to functional impairment of the MBL pathway and the presence of anti-MBL autoantibodies were reported earlier in rheumatoid arthritis (RA). MBL was observed to be S-nitrosylated (S-nitrosated) in vitro. HepG2 cells were stimulated with 10% synovial fluid from RA patients to produce increased levels of MBL and nitric oxide. Under these experimental conditions MBL was observed to be S-nitrosated using biotin switch assay. The plasma of RA patients was also found to contain higher levels of S-nitrosylated MBL (SNO-MBL) in comparison to the healthy controls. Functional activities of SNO-MBL were compared with normal MBL. Mannan binding and C4 deposition ability of MBL was found to decrease after S-nitrosylation. It was also observed that S-nitrosylation of MBL leads to a decrease in the bacterial phagocytosis and apoptotic cell binding as measured by fluorescence microscopy and FACS analysis. These results indicate that the carbohydrate binding ability of MBL was affected by S-nitrosylation (S-nitrosation). High levels of anti-MBL autoantibodies were detected against SNO-MBL in plasma of RA patients in comparison to normal MBL suggesting a role of SNO-MBL in generation of autoantibodies in RA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agglutination
  • Apoptosis / drug effects
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism*
  • Autoantibodies / immunology*
  • Biotin
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • Mannose-Binding Lectins / chemistry*
  • Mannose-Binding Lectins / metabolism*
  • Nitrogen / chemistry*
  • Phagocytosis / drug effects
  • Phorbol Esters / pharmacology

Substances

  • Autoantibodies
  • Mannose-Binding Lectins
  • Phorbol Esters
  • Biotin
  • Nitrogen