The extracellular matrix and inflammation - Fibromodulin activates the classical pathway of complement by directly binding C1q

Research output: Contribution to journalArticle

Abstract

Components that propagate inflammation in joint disease may be derived from cartilage since the inflammation resolves after joint replacement. We found that the cartilage component fibromodulin has the ability to activate an inflammatory cascade, i.e. complement. Fibromodulin and immunoglobulins cause comparable deposition of C1q, C4b, and C3b from human serum. Using C1q and factor B-deficient sera in combination with varying contents of metal ions, we established that fibromodulin activates both the classical and the alternative pathways of complement. Further studies revealed that fibromodulin binds directly to the globular heads of C1q, leading to activation of C1. However, deposition of the membrane attack complex and C5a release were lower in the presence of fibromodulin as compared with IgG. This can be explained by the fact that fibromodulin also binds complement inhibitor factor H. Factor H and C1q bind to non-overlapping sites on fibromodulin, but none of the interactions is mediated by the negatively charged keratan sulfate substituents of fibromodulin. C1q but not factor H binds to an N-terminal fragment of fibromodulin previously implicated to be affected in cartilage stimulated with the inflammatory cytokine interleukin 1. Taken together our observations indicate fibromodulin as one factor involved in the sustained inflammation of the joint.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Clinical Medicine
  • Rheumatology and Autoimmunity
Original languageEnglish
Pages (from-to)32301-32308
JournalJournal of Biological Chemistry
Volume280
Issue number37
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Translational Medicine (013017500), Connective Tissue Biology (013230151), Protein Chemistry (013017510), Clinical Chemistry, Malmö (013016000), Division of Infection Medicine (BMC) (013024020)

Related research output

Andreas Holmér, 2007, Clinical Chemistry, Malmö. 167 p.

Research output: ThesisDoctoral Thesis (compilation)

View all (1)