C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation

After cell death, via apoptosis or necrosis, the uptake of dead cells by neighboring cells or phagocytes prevents the release of intracellular content. An array of molecules, including initiation molecules of the complement system, are involved in marking dead cells for uptake. After binding of thes...

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Main Authors:	Trouw, Leendert A., Nilsson, Sara C., Gonçalves, Isabel, Landberg, Göran, Blom, Anna M.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2005
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212022/

id	pubmed-2212022
recordtype	oai_dc
spelling	pubmed-22120222008-03-11 C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation Trouw, Leendert A. Nilsson, Sara C. Gonçalves, Isabel Landberg, Göran Blom, Anna M. Article After cell death, via apoptosis or necrosis, the uptake of dead cells by neighboring cells or phagocytes prevents the release of intracellular content. An array of molecules, including initiation molecules of the complement system, are involved in marking dead cells for uptake. After binding of these molecules, complement activation takes place, which when uncontrolled might result in a proinflammatory state. In the current study we demonstrate that complement inhibitor, C4b-binding protein (C4BP), binds strongly to necrotic cells, irrespective of the cell type used or the method of induction. After binding of the C4BP–protein S (PS) complex to necrotic cells via PS-phosphatidylserine and C4BP-DNA interactions, C4BP-PS inhibits complement activation on these cells. C4BP binds DNA via a patch of positively charged amino acids, mainly on the second complement control domain of the C4BP α-chain (affinity constant: 190 nM). Furthermore, C4BP limits DNA release from necrotic cells and inhibits DNA-mediated complement activation in solution. The C4BP–necrotic cell interaction also occurs in vivo as necrotic areas of arteriosclerotic plaques and of various cancers stain strongly positive for C4BP. This study describes a novel mechanism in which C4BP limits the inflammatory potential of necrotic cells. The Rockefeller University Press 2005-06-20 /pmc/articles/PMC2212022/ /pubmed/15967823 http://dx.doi.org/10.1084/jem.20050189 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Trouw, Leendert A. Nilsson, Sara C. Gonçalves, Isabel Landberg, Göran Blom, Anna M.
spellingShingle	Trouw, Leendert A. Nilsson, Sara C. Gonçalves, Isabel Landberg, Göran Blom, Anna M. C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation
author_facet	Trouw, Leendert A. Nilsson, Sara C. Gonçalves, Isabel Landberg, Göran Blom, Anna M.
author_sort	Trouw, Leendert A.
title	C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation
title_short	C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation
title_full	C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation
title_fullStr	C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation
title_full_unstemmed	C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation
title_sort	c4b-binding protein binds to necrotic cells and dna, limiting dna release and inhibiting complement activation
description	After cell death, via apoptosis or necrosis, the uptake of dead cells by neighboring cells or phagocytes prevents the release of intracellular content. An array of molecules, including initiation molecules of the complement system, are involved in marking dead cells for uptake. After binding of these molecules, complement activation takes place, which when uncontrolled might result in a proinflammatory state. In the current study we demonstrate that complement inhibitor, C4b-binding protein (C4BP), binds strongly to necrotic cells, irrespective of the cell type used or the method of induction. After binding of the C4BP–protein S (PS) complex to necrotic cells via PS-phosphatidylserine and C4BP-DNA interactions, C4BP-PS inhibits complement activation on these cells. C4BP binds DNA via a patch of positively charged amino acids, mainly on the second complement control domain of the C4BP α-chain (affinity constant: 190 nM). Furthermore, C4BP limits DNA release from necrotic cells and inhibits DNA-mediated complement activation in solution. The C4BP–necrotic cell interaction also occurs in vivo as necrotic areas of arteriosclerotic plaques and of various cancers stain strongly positive for C4BP. This study describes a novel mechanism in which C4BP limits the inflammatory potential of necrotic cells.
publisher	The Rockefeller University Press
publishDate	2005
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212022/
_version_	1611433980944449536

C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation

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