Binding of interferon gamma by glycosaminoglycans: a strategy for localization and/or inhibition of its activity.
Glycosaminoglycans (GAGs) are a group of negatively charged molecules present in many tissues as components of the extracellular matrix, basement and cellular membranes. This work analysed the ability of this group of substances to interact with human interferon gamma and the effect of those interactions on its biologic activity. A variety of GAGs (heparin, heparan sulfate, chondroitin sulfate and hyaluronic acid), and a related sulfated polysaccharide (dextran sulfate), were found to interact with IFN-gamma as determined by inhibition of the binding of [125I]IFN-gamma to COLO-205 cells and binding to wells coated with GAGs. These interactions were inhibited by synthetic peptides mimicking the sequences of the basic amino acid cluster located at the C-terminal end of mouse and human IFN-gamma, or by poly-L-lysine, suggesting that ionic interactions between the positively-charged C-terminus and negatively charged groups in GAGs were involved. IFN-gamma molecules bound to plate-immobilized or endothelial cell surface GAGs retained biological activity, since they could induce major histocompatibility complex (MHC) class II expression on COLO-205 cells, suggesting that cell surface GAGs might be able to present IFN-gamma to its receptors. These results suggest important regulatory roles for GAGs on the activity of IFN-gamma in vivo.
D000818:Animals; D000917:Antibody Formation; D001667:Binding, Competitive; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000378:metabolism*; D007457:Iodine Radioisotopes; D051379:Mice; D011485:Protein Binding; D012995:Solubility; D014407:Tumor Cells, Cultured