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Complement regulation in human atherosclerotic coronary lesions - Immunohistochemical evidence that C4b-binding protein negatively regulates the classical complement pathway, and that C5b-9 is formed via the alternative complement pathway

Oksjoki, Riina; Kovanen, Petri T.; Mayranpaa, Mikko I.; Laine, Petri; Blom, Anna LU ; Meri, Seppo and Pentikainen, Markku O. (2007) In Atherosclerosis 192(1). p.40-48
Abstract
Objective: The complement system is activated in human atherosclerotic lesions and may hence aggravate local inflammation. We studied the presence and localization of C4b-binding protein (C4bp), the major inhibitor of the classical complement pathway, in human atherosclerotic lesions in relation to complement activation products and protein S, which circulates in complex with C4bp. Methods and results: Immunohistochemistry, of human coronary arteries showed C4bp to be virtually absent in normal arteries but present in early and advanced atherosclerotic lesions. In the lesions, C4bp is associated with proteoglycans, and affinity chromatography showed that C4bp interacts with human arterial proteoglycans. Areas containing C4bp also contained... (More)
Objective: The complement system is activated in human atherosclerotic lesions and may hence aggravate local inflammation. We studied the presence and localization of C4b-binding protein (C4bp), the major inhibitor of the classical complement pathway, in human atherosclerotic lesions in relation to complement activation products and protein S, which circulates in complex with C4bp. Methods and results: Immunohistochemistry, of human coronary arteries showed C4bp to be virtually absent in normal arteries but present in early and advanced atherosclerotic lesions. In the lesions, C4bp is associated with proteoglycans, and affinity chromatography showed that C4bp interacts with human arterial proteoglycans. Areas containing C4bp also contained IgM and C4 suggesting that C4bp is involved in the regulation of the classical complement pathway. However, C5b-9 was virtually absent in these areas but, instead, colocalized with properdin deeper in the intima, suggesting that C5b-9 is formed by the alternative complement pathway. A fraction of C4bp was associated with protein S and apoptotic cells. Conclusions: The results indicate that C4bp regulates the classical complement pathway in human atherosclerotic lesions. Thus, unlike the alternative pathway, the classical complement pathway does not generate C5b-9, but is likely to be involved in the clean-up of apoptotic cells and cell debris in the arterial intima. (c) 2006 Elsevier Ireland Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C4b-binding protein, inflammation, complement, atherosclerosis
in
Atherosclerosis
volume
192
issue
1
pages
40 - 48
publisher
Elsevier
external identifiers
  • wos:000246655400006
  • scopus:34247123226
ISSN
1879-1484
DOI
10.1016/j.atherosclerosis.2006.06.013
language
English
LU publication?
yes
id
987ac297-6940-4ca5-9528-7cd84f861356 (old id 659707)
date added to LUP
2007-12-19 10:15:08
date last changed
2017-11-05 03:33:56
@article{987ac297-6940-4ca5-9528-7cd84f861356,
  abstract     = {Objective: The complement system is activated in human atherosclerotic lesions and may hence aggravate local inflammation. We studied the presence and localization of C4b-binding protein (C4bp), the major inhibitor of the classical complement pathway, in human atherosclerotic lesions in relation to complement activation products and protein S, which circulates in complex with C4bp. Methods and results: Immunohistochemistry, of human coronary arteries showed C4bp to be virtually absent in normal arteries but present in early and advanced atherosclerotic lesions. In the lesions, C4bp is associated with proteoglycans, and affinity chromatography showed that C4bp interacts with human arterial proteoglycans. Areas containing C4bp also contained IgM and C4 suggesting that C4bp is involved in the regulation of the classical complement pathway. However, C5b-9 was virtually absent in these areas but, instead, colocalized with properdin deeper in the intima, suggesting that C5b-9 is formed by the alternative complement pathway. A fraction of C4bp was associated with protein S and apoptotic cells. Conclusions: The results indicate that C4bp regulates the classical complement pathway in human atherosclerotic lesions. Thus, unlike the alternative pathway, the classical complement pathway does not generate C5b-9, but is likely to be involved in the clean-up of apoptotic cells and cell debris in the arterial intima. (c) 2006 Elsevier Ireland Ltd. All rights reserved.},
  author       = {Oksjoki, Riina and Kovanen, Petri T. and Mayranpaa, Mikko I. and Laine, Petri and Blom, Anna and Meri, Seppo and Pentikainen, Markku O.},
  issn         = {1879-1484},
  keyword      = {C4b-binding protein,inflammation,complement,atherosclerosis},
  language     = {eng},
  number       = {1},
  pages        = {40--48},
  publisher    = {Elsevier},
  series       = {Atherosclerosis},
  title        = {Complement regulation in human atherosclerotic coronary lesions - Immunohistochemical evidence that C4b-binding protein negatively regulates the classical complement pathway, and that C5b-9 is formed via the alternative complement pathway},
  url          = {http://dx.doi.org/10.1016/j.atherosclerosis.2006.06.013},
  volume       = {192},
  year         = {2007},
}