Galectin-3 binds highly galactosylated IgG1 and is crucial for the IgG1 complex mediated inhibition of C5aReceptor induced immune responses.
Changes in the glycosylation of immunoglobulins have been shown to modulate immune homeostasis and disease pathology. In this sense it has been shown that highly galactosylated but not agalactosylated IgG1 immune complexes (ICs) inhibit C5aR-mediated pro-inflammatory immune responses via the assembly of FcγRIIB-Dectin-1 receptor complexes. In this study we demonstrated that Galectin-3, a galactose-binding lectin that is known to cross-link proteins on cell-surfaces via binding their N-glycans, bound to highly-galactosylated, but not agalactosylated IgG1. Further, Galectin-3 was essential for the IC-mediated inhibition of C5a-induced neutrophil chemotaxis in vitro. Taken together our results indicate that Galectin-3 mediates the interaction of ICs with the FcγRIIB-Dectin-1 receptor complex for delivering immunoregulatory signals to inhibit C5aR-mediated immune responses.
Septomics Research Center, Jena University Hospital, Albert-Einstein-Str. 10, D-07745 Jena, Germany.
Kerstin A
KA
Heyl
Institute for Systemic Inflammation Research, University of Lübeck, Ratzeburger Allee 160, D-23562 Lübeck, Germany.
Christian M
CM
Karsten
Septomics Research Center, Jena University Hospital, Albert-Einstein-Str. 10, D-07745 Jena, Germany. Electronic address: hortense.slevogt@med.uni-jena.de.
Hortense
H
Slevogt
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005690:Galactose / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D056892:Mediator Complex / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000099181:Dectin-1
D000936:Antigen-Antibody Complex; D005690:Galactose; D037502:Galectin 3; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D056892:Mediator Complex; D044087:Receptor, Anaphylatoxin C5a; D017452:Receptors, IgG; D000099181:Dectin-1; C499172:Fcgr2b protein, mouse
Fc FcγRIIB-Dectin-1 receptor complex; Galectin-3; IgG1 immune complexes; Neutrophil chemotaxis