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.
Keywords
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Article info
Publication history
Published online: July 18, 2006
Accepted:
June 2,
2006
Received in revised form:
June 2,
2006
Received:
March 10,
2006
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
