Complement Inhibitor C4b-Binding Protein Interacts Directly with Small Glycoproteins of the Extracellular Matrix

摘要: Components derived from cartilage have been suggested to maintain the inflammation in joints arthritis. Small leucine-rich repeat proteins (SLRPs) are structural components of important organizing meshwork extracellular matrix components. It has recently shown that SLRP fibromodulin interacts with complement initiator C1q, leading activation. The response is limited since also inhibitor factor H. We now found osteoadherin, chondroadherin, fibromodulin, and proline arginine-rich end protein bind C4b-binding (C4BP). Using direct binding assays C4BP fragments mutants lacking individual domains combination electron microscopy, we demonstrated mainly central core mediated SLRPs. Binding SLRPs did not affect its ability inhibit complement. Osteoadherin, which C1q activate complement, were cause significantly higher C9 deposition C4BP-depleted serum compared Igs, indicating level activation initiated by regulated simultaneous C4BP. A similar dual inhibitors was observed previously for other endogenous ligands (amyloid, prions, C-reactive protein, apoptotic cells) but exogenous activators (bacteria-bound Igs). These interactions can be significant during inflammatory joint diseases, such as rheumatoid arthritis, where degraded, released into synovial fluid, they interact factors system.