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Serglycin inhibits the classical and lectin pathways of complement via its glycosaminoglycan chains: Implications for multiple myeloma

På svenska

Author

  • Antonis Skliris
  • Kaisa Happonen
  • Evangelos Terpos
  • Vassiliki Labropoulou
  • Magne Borset
  • Dick Heinegård
  • Anna Blom
  • Achilleas D. Theocharis

Summary, in English

Serglycin (SG) is a proteoglycan expressed by hematopoietic cells and is constitutively secreted by multiple myeloma (MM) cells. SG participates in the regulation of various inflammatory events. We found that SG secreted by human MM cell lines inhibits both the classical and lectin pathways of complement, without influencing alternative pathway activity. The inhibitory effect of SG is due to direct interactions with C1q and mannose-binding lectin (MBL). C1q-binding is mediated through the glycosaminoglycan moieties of SG, whereas MBL binds additionally to SG protein core. Interactions between SG and C1q as well as MBL are diminished in the presence of chondroitin sulfate type E. In addition, we localized the SG-binding site to the collagen-like stalk of C1q. Interactions between SG and C1q as well as MBL are ionic in character and only the interaction with MBL was found to be partially dependent on the presence of calcium. We found the serum levels of SG to be elevated in patients with MM compared to healthy controls. Moreover, we found that SG expressed from myeloma plasma cells protects these cells from complement activation induced by treatment with anti-thymocyte immunoglobulins. This might protect myeloma cells during immunotherapy and promote survival of malignant cells.

Department/s

Publishing year

2011

Language

English

Pages

437-449

Publication/Series

European Journal of Immunology

Volume

41

Issue

2

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Immunology in the medical area

Keywords

  • Complement
  • Multiple myeloma
  • Serglycin

Status

Published

Research group

  • Protein Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1521-4141