The C-type lectin of the aggrecan g3 domain activates complement.

Camilla Melin Fürst, Matthias Mörgelin, Kasper Vadstrup, Dick Heinegård, Anders Aspberg, Anna Blom

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Excessive complement activation contributes to joint diseases such as rheumatoid arthritis and osteoarthritis during which cartilage proteins are fragmented and released into the synovial fluid. Some of these proteins and fragments activate complement, which may sustain inflammation. The G3 domain of large cartilage proteoglycan aggrecan interacts with other extracellular matrix proteins, fibulins and tenascins, via its C-type lectin domain (CLD) and has important functions in matrix organization. Fragments containing G3 domain are released during normal aggrecan turnover, but increasingly so in disease. We now show that the aggrecan CLD part of the G3 domain activates the classical and to a lesser extent the alternative pathway of complement, via binding of C1q and C3, respectively. The complement control protein (CCP) domain adjacent to the CLD showed no effect on complement initiation. The binding of C1q to G3 depended on ionic interactions and was decreased in D2267N mutant G3. However, the observed complement activation was attenuated due to binding of complement inhibitor factor H to CLD and CCP domains. This was most apparent at the level of deposition of terminal complement components. Taken together our observations indicate aggrecan CLD as one factor involved in the sustained inflammation of the joint.
Original languageEnglish
Article numbere61407
JournalPLoS ONE
Issue number4
Publication statusPublished - 2013

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Connective Tissue Biology (013230151), Division of Infection Medicine (BMC) (013024020), Protein Chemistry (013017510)

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity
  • Infectious Medicine
  • Other Basic Medicine


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