S-nitrosylation of mannose binding lectin regulates its functional activities and the formation of autoantibody in rheumatoid arthritis.
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.
Gupta
Bhawna
B
Proteomics and Structural Biology Division, Institute of Genomics & Integrative Biology, Delhi University Campus, Mall Road, Delhi 110 007, India.
Raghav
Sunil K
SK
Das
Hasi R
HR
D000371:Agglutination; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001323:Autoantibodies / Q000276:immunology*; D001710:Biotin; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D037241:Mannose-Binding Lectins / Q000737:chemistry* / Q000378:metabolism*; D009584:Nitrogen / Q000737:chemistry*; D010587:Phagocytosis / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology
D001323:Autoantibodies; D037241:Mannose-Binding Lectins; D010703:Phorbol Esters; D001710:Biotin; D009584:Nitrogen