PRELP Protein Inhibits the Formation of the Complement Membrane Attack Complex
Happonen, Kaisa LU ; Melin Fürst, Camilla LU ; Saxne, Tore LU ; Heinegård, Dick LU and Blom, Anna LU
(2012)
In Journal of Biological Chemistry
287(11).
p.8092-8100
- Abstract
- PRELP is a 58-kDa proteoglycan found in a variety of extracellular matrices, including cartilage and at several basement membranes. In rheumatoid arthritis (RA), the cartilage tissue is destroyed and fragmented molecules, including PRELP, are released into the synovial fluid where they may interact with components of the complement system. In a previous study, PRELP was found to interact with the complement inhibitor C4b-binding protein, which was suggested to locally down-regulate complement activation in joints during RA. Here we show that PRELP directly inhibits all pathways of complement by binding C9 and thereby prevents the formation of the membrane attack complex (MAC). PRELP does not interfere with the interaction between C9 and... (More)
- PRELP is a 58-kDa proteoglycan found in a variety of extracellular matrices, including cartilage and at several basement membranes. In rheumatoid arthritis (RA), the cartilage tissue is destroyed and fragmented molecules, including PRELP, are released into the synovial fluid where they may interact with components of the complement system. In a previous study, PRELP was found to interact with the complement inhibitor C4b-binding protein, which was suggested to locally down-regulate complement activation in joints during RA. Here we show that PRELP directly inhibits all pathways of complement by binding C9 and thereby prevents the formation of the membrane attack complex (MAC). PRELP does not interfere with the interaction between C9 and already formed C5b-8, but inhibits C9 polymerization thereby preventing formation of the lytic pore. The alternative pathway is moreover inhibited already at the level of C3-convertase formation due to an interaction between PRELP and C3. This suggests that PRELP may down-regulate complement attack at basement membranes and on damaged cartilage and therefore limit pathological complement activation in inflammatory disease such as RA. The net outcome of PRELP-mediated complement inhibition will highly depend on the local concentration of other complement modulating molecules as well as on the local concentration of available complement proteins. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2515553
- author
- Happonen, Kaisa
LU
; Melin Fürst, Camilla
LU
; Saxne, Tore
LU
; Heinegård, Dick
LU
and Blom, Anna
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 287
- issue
- 11
- pages
- 8092 - 8100
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000301349400025
- pmid:22267731
- scopus:84858009778
- pmid:22267731
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M111.291476
- 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: Protein Chemistry (013017510), Connective Tissue Biology (013230151)
- id
- 233026bc-6853-472f-8868-476e25a34392 (old id 2515553)
- date added to LUP
- 2016-04-01 10:16:10
- date last changed
- 2022-05-17 21:26:27
@article{233026bc-6853-472f-8868-476e25a34392,
abstract = {{PRELP is a 58-kDa proteoglycan found in a variety of extracellular matrices, including cartilage and at several basement membranes. In rheumatoid arthritis (RA), the cartilage tissue is destroyed and fragmented molecules, including PRELP, are released into the synovial fluid where they may interact with components of the complement system. In a previous study, PRELP was found to interact with the complement inhibitor C4b-binding protein, which was suggested to locally down-regulate complement activation in joints during RA. Here we show that PRELP directly inhibits all pathways of complement by binding C9 and thereby prevents the formation of the membrane attack complex (MAC). PRELP does not interfere with the interaction between C9 and already formed C5b-8, but inhibits C9 polymerization thereby preventing formation of the lytic pore. The alternative pathway is moreover inhibited already at the level of C3-convertase formation due to an interaction between PRELP and C3. This suggests that PRELP may down-regulate complement attack at basement membranes and on damaged cartilage and therefore limit pathological complement activation in inflammatory disease such as RA. The net outcome of PRELP-mediated complement inhibition will highly depend on the local concentration of other complement modulating molecules as well as on the local concentration of available complement proteins.}},
author = {{Happonen, Kaisa and Melin Fürst, Camilla and Saxne, Tore and Heinegård, Dick and Blom, Anna}},
issn = {{1083-351X}},
language = {{eng}},
number = {{11}},
pages = {{8092--8100}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{PRELP Protein Inhibits the Formation of the Complement Membrane Attack Complex}},
url = {{https://lup.lub.lu.se/search/files/1699383/2539426.pdf}},
doi = {{10.1074/jbc.M111.291476}},
volume = {{287}},
year = {{2012}},
}