Alexander Denesyuk,§ Uwe Hansen,¶ Yrjö Konttinen,# Mark S. Johnson,§. Rikard Holmdahl,â ,â¡ and Jyrki Heino*,1. *Department of Biochemistry and â Medicity ...
The FASEB Journal • Research Communication
Citrullination of collagen II affects integrin-mediated cell adhesion in a receptor-specific manner Kalle Sipilä,* Sabrina Haag,‡ Konstantin Denessiouk,§ Jarmo Käpylä,* Eric C. Peters,储 Alexander Denesyuk,§ Uwe Hansen,¶ Yrjö Konttinen,# Mark S. Johnson,§ Rikard Holmdahl,†,‡ and Jyrki Heino*,1 *Department of Biochemistry and †Medicity Research Laboratory, University of Turku, Turku, Finland; ‡ Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden, §Structural Bioinformatics Laboratory, Biochemistry, Department of Bioscience, Åbo Akademi University, Turku, Finland, 储Genomics Institute of the Novartis Research Foundation, San Diego, California, USA; ¶Department of Physiology, Chemistry, and Pathobiochemistry, Muenster University Hospital, Muenster, Germany; and #Department of Medicine, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland Citrullinated collagen II (CII) is a wellknown autoantigen in rheumatoid arthritis (RA). However, the direct effects of CII citrullination on cell behavior have not been described. To study whether citrullination of CII could affect cellular functions, we measured the adhesion of 3 different cell types (human Saos2 osteosarcoma cells, human synovial fibroblasts, and rat mesenchymal stem cells) with impedance-based technology. The binding of different collagen receptor integrins to citrullinated collagen was studied by CHO cell lines, each overexpressing 1 of the 4 human collagen receptors on the cell surface, and with solidphase binding assays, using the recombinant human integrin ␣1I, ␣2I, ␣10I, and ␣11I domains. Collagen citrullination decreased the adhesion of synovial fibroblasts ⬃50% (P
