Linked Life Data

19155499

Source:http://linkedlifedata.com/resource/pubmed/id/19155499

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-1-21
pubmed:abstractText
Components derived from cartilage have been suggested to maintain the inflammation in joints in arthritis. Small leucine-rich repeat proteins (SLRPs) are structural components of cartilage important in organizing the meshwork of extracellular matrix components. It has recently been shown that the SLRP fibromodulin interacts with complement initiator C1q, leading to complement activation. The complement response is limited since fibromodulin also interacts with the complement inhibitor factor H. We have now found that osteoadherin, chondroadherin, fibromodulin, and proline arginine-rich end leucine-rich repeat protein bind to the complement inhibitor C4b-binding protein (C4BP). Using direct binding assays with C4BP fragments and C4BP mutants lacking individual domains in combination with electron microscopy, we have demonstrated that mainly the central core of C4BP mediated binding to SLRPs. Binding of SLRPs to C4BP did not affect its ability to inhibit complement. Osteoadherin, fibromodulin, and chondroadherin, which bind C1q and activate complement, were found to cause significantly higher C9 deposition in C4BP-depleted serum compared with Igs, indicating that the level of complement activation initiated by SLRPs is regulated by simultaneous binding to C4BP. A similar dual binding of C1q and complement inhibitors was observed previously for other endogenous ligands (amyloid, prions, C-reactive protein, and apoptotic cells) but not for exogenous activators (bacteria-bound Igs). These interactions can be significant during inflammatory joint diseases, such as rheumatoid arthritis, where cartilage is degraded, and cartilage components are released into synovial fluid, where they can interact with factors of the complement system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/COL11A2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type XI, http://linkedlifedata.com/resource/pubmed/chemical/Complement C4b-Binding Protein, http://linkedlifedata.com/resource/pubmed/chemical/Complement Inactivating Agents, http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/PRELP protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Protein S, http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans, http://linkedlifedata.com/resource/pubmed/chemical/chondroadherin, http://linkedlifedata.com/resource/pubmed/chemical/fibromodulin, http://linkedlifedata.com/resource/pubmed/chemical/osteoadherin
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
182
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1518-25
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Complement inhibitor C4b-binding protein interacts directly with small glycoproteins of the extracellular matrix.
pubmed:affiliation
Department of Laboratory Medicine, Wallenberg Laboratory, University Hospital Malmö, Lund University, Malmö, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't