Regulation of complement by COMP allows for a novel molecular diagnostic principle in rheumatoid arthritis.
Happonen, Kaisa LU ; Saxne, Tore LU ; Aspberg, Anders LU
; Mörgelin, Matthias
LU
; Heinegård, Dick
LU
and Blom, Anna
LU
(2010)
In Arthritis and Rheumatism
62(12).
p.3574-3583
- Abstract
- OBJECTIVE:: Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint diseases, such as rheumatoid arthritis (RA) and osteoarthritis (OA). In this study we investigated the ability of COMP to regulate complement. Such capacity was previously shown for some cartilage proteins. METHODS:: Regulation of complement by COMP was studied using functional assays in vitro. Interactions between complement proteins and COMP were investigated using direct binding assays and electron microscopy. Circulating COMP and COMP-C3b complexes in serum and synovial fluid from RA and... (More)
- OBJECTIVE:: Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint diseases, such as rheumatoid arthritis (RA) and osteoarthritis (OA). In this study we investigated the ability of COMP to regulate complement. Such capacity was previously shown for some cartilage proteins. METHODS:: Regulation of complement by COMP was studied using functional assays in vitro. Interactions between complement proteins and COMP were investigated using direct binding assays and electron microscopy. Circulating COMP and COMP-C3b complexes in serum and synovial fluid from RA and OA patients and healthy controls were measured using a novel ELISA. RESULTS:: We show in vivo evidence of complement activation by released COMP in the general circulation of patients with RA, but not OA patients. We found that COMP induces activation and deposition of C3b and C9 specifically via the alternative pathway of complement, which is attributable to a direct interaction between COMP and properdin. Furthermore, COMP inhibits the classical and the lectin complement pathways due to direct interaction with the stalk region of C1q and mannose-binding lectin, respectively. CONCLUSION:: COMP is the first extracellular matrix protein for which an active role is demonstrated in inflammation in vivo where it can activate one complement pathway at the same time as it has the potential to inhibit another. The net outcome of these interactions is most likely determined by the type of released COMP-fragments, which may be disease-specific. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1665018
- author
- Happonen, Kaisa
LU
; Saxne, Tore
LU
; Aspberg, Anders
LU
; Mörgelin, Matthias
LU
; Heinegård, Dick
LU
and Blom, Anna
LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Arthritis and Rheumatism
- volume
- 62
- issue
- 12
- pages
- 3574 - 3583
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:20737467
- wos:000285210200010
- pmid:20737467
- scopus:78650070714
- ISSN
- 1529-0131
- DOI
- 10.1002/art.27720
- language
- English
- LU publication?
- yes
- id
- ecf1f671-3d1f-44fa-b3e0-56f2b27e5b95 (old id 1665018)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20737467?dopt=Abstract
- date added to LUP
- 2016-04-01 09:48:14
- date last changed
- 2022-05-13 01:44:07
@article{ecf1f671-3d1f-44fa-b3e0-56f2b27e5b95,
abstract = {{OBJECTIVE:: Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint diseases, such as rheumatoid arthritis (RA) and osteoarthritis (OA). In this study we investigated the ability of COMP to regulate complement. Such capacity was previously shown for some cartilage proteins. METHODS:: Regulation of complement by COMP was studied using functional assays in vitro. Interactions between complement proteins and COMP were investigated using direct binding assays and electron microscopy. Circulating COMP and COMP-C3b complexes in serum and synovial fluid from RA and OA patients and healthy controls were measured using a novel ELISA. RESULTS:: We show in vivo evidence of complement activation by released COMP in the general circulation of patients with RA, but not OA patients. We found that COMP induces activation and deposition of C3b and C9 specifically via the alternative pathway of complement, which is attributable to a direct interaction between COMP and properdin. Furthermore, COMP inhibits the classical and the lectin complement pathways due to direct interaction with the stalk region of C1q and mannose-binding lectin, respectively. CONCLUSION:: COMP is the first extracellular matrix protein for which an active role is demonstrated in inflammation in vivo where it can activate one complement pathway at the same time as it has the potential to inhibit another. The net outcome of these interactions is most likely determined by the type of released COMP-fragments, which may be disease-specific.}},
author = {{Happonen, Kaisa and Saxne, Tore and Aspberg, Anders and Mörgelin, Matthias and Heinegård, Dick and Blom, Anna}},
issn = {{1529-0131}},
language = {{eng}},
number = {{12}},
pages = {{3574--3583}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Arthritis and Rheumatism}},
title = {{Regulation of complement by COMP allows for a novel molecular diagnostic principle in rheumatoid arthritis.}},
url = {{http://dx.doi.org/10.1002/art.27720}},
doi = {{10.1002/art.27720}},
volume = {{62}},
year = {{2010}},
}