Complement inhibitor C4b-binding protein interacts directly with small glycoproteins of the extracellular matrix.
Happonen, Kaisa LU ; Holmér, Andreas LU ; Mörgelin, Matthias LU ; Heinegård, Dick LU and Blom, Anna LU
(2009)
In Journal of immunology
182(3).
p.1518-1525
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1289483
- author
- Happonen, Kaisa
LU
; Holmér, Andreas
LU
; Mörgelin, Matthias
LU
; Heinegård, Dick
LU
and Blom, Anna
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of immunology
- volume
- 182
- issue
- 3
- pages
- 1518 - 1525
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000262842100036
- pmid:19155499
- scopus:63149095644
- ISSN
- 1550-6606
- language
- English
- LU publication?
- yes
- additional info
- 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), Clinical Chemistry, Malmö (013016000), Protein Chemistry (013017510)
- id
- 976ec250-f8eb-4f2e-8f37-ecb3c8e83a3f (old id 1289483)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19155499?dopt=Abstract
- date added to LUP
- 2016-04-04 09:21:16
- date last changed
- 2022-04-15 22:54:28
@article{976ec250-f8eb-4f2e-8f37-ecb3c8e83a3f,
abstract = {{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.}},
author = {{Happonen, Kaisa and Holmér, Andreas and Mörgelin, Matthias and Heinegård, Dick and Blom, Anna}},
issn = {{1550-6606}},
language = {{eng}},
number = {{3}},
pages = {{1518--1525}},
publisher = {{American Association of Immunologists}},
series = {{Journal of immunology}},
title = {{Complement inhibitor C4b-binding protein interacts directly with small glycoproteins of the extracellular matrix.}},
url = {{http://www.ncbi.nlm.nih.gov/pubmed/19155499?dopt=Abstract}},
volume = {{182}},
year = {{2009}},
}