C4b-binding protein: The good, the bad and the deadly. Novel functions of an old friend.
Ermert, David LU and Blom, Anna LU
(2016)
In Immunology Letters
169.
p.82-92
- Abstract
- C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75kDa α-chains and often also one 40kDa β-chain, both of which are mainly composed of complement control protein (CCP) domains. Structure-function studies revealed that one crucial binding site responsible for inhibition of complement is located to CCP1-3 of the α-chain. Binding of anticoagulant protein S to the CCP1 of the β-chain provides C4BP with the ability to strongly bind apoptotic and necrotic cells in order to prevent inflammation arising from activation... (More)
- C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75kDa α-chains and often also one 40kDa β-chain, both of which are mainly composed of complement control protein (CCP) domains. Structure-function studies revealed that one crucial binding site responsible for inhibition of complement is located to CCP1-3 of the α-chain. Binding of anticoagulant protein S to the CCP1 of the β-chain provides C4BP with the ability to strongly bind apoptotic and necrotic cells in order to prevent inflammation arising from activation of complement by these cells. Further, C4BP interacts strongly with various types of amyloid and enhances fibrillation of islet amyloid polypeptide secreted from pancreatic beta cells, which may attenuate pro-inflammatory and cytotoxic effects of this amyloid. Full deficiency of C4BP has not been identified but non-synonymous alterations in its sequence have been found in haemolytic uremic syndrome and recurrent pregnancy loss. Furthermore, C4BP is bound by several bacterial pathogens, notably Streptococcus pyogenes, which due to inhibition of complement and enhancement of bacterial adhesion to endothelial cells provides these bacteria with a survival advantage in the host. Thus, depending on the context, C4BP has a protective or detrimental role in the organism. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8505131
- author
- Ermert, David
LU
and Blom, Anna
LU
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Immunology Letters
- volume
- 169
- pages
- 82 - 92
- publisher
- Elsevier
- external identifiers
-
- pmid:26658464
- scopus:84949908683
- wos:000369205200010
- pmid:26658464
- ISSN
- 0165-2478
- DOI
- 10.1016/j.imlet.2015.11.014
- language
- English
- LU publication?
- yes
- id
- ba1e9f95-5580-492f-b989-0b0973710d7a (old id 8505131)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26658464?dopt=Abstract
- date added to LUP
- 2016-04-04 08:55:26
- date last changed
- 2022-05-16 22:17:56
@article{ba1e9f95-5580-492f-b989-0b0973710d7a,
abstract = {{C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75kDa α-chains and often also one 40kDa β-chain, both of which are mainly composed of complement control protein (CCP) domains. Structure-function studies revealed that one crucial binding site responsible for inhibition of complement is located to CCP1-3 of the α-chain. Binding of anticoagulant protein S to the CCP1 of the β-chain provides C4BP with the ability to strongly bind apoptotic and necrotic cells in order to prevent inflammation arising from activation of complement by these cells. Further, C4BP interacts strongly with various types of amyloid and enhances fibrillation of islet amyloid polypeptide secreted from pancreatic beta cells, which may attenuate pro-inflammatory and cytotoxic effects of this amyloid. Full deficiency of C4BP has not been identified but non-synonymous alterations in its sequence have been found in haemolytic uremic syndrome and recurrent pregnancy loss. Furthermore, C4BP is bound by several bacterial pathogens, notably Streptococcus pyogenes, which due to inhibition of complement and enhancement of bacterial adhesion to endothelial cells provides these bacteria with a survival advantage in the host. Thus, depending on the context, C4BP has a protective or detrimental role in the organism.}},
author = {{Ermert, David and Blom, Anna}},
issn = {{0165-2478}},
language = {{eng}},
pages = {{82--92}},
publisher = {{Elsevier}},
series = {{Immunology Letters}},
title = {{C4b-binding protein: The good, the bad and the deadly. Novel functions of an old friend.}},
url = {{https://lup.lub.lu.se/search/files/8162428/5210800.pdf}},
doi = {{10.1016/j.imlet.2015.11.014}},
volume = {{169}},
year = {{2016}},
}