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The C4b-binding protein-protein S complex inhibits the phagocytosis of apoptotic cells.

Kask, Lena LU ; Trouw, Leendert LU ; Dahlbäck, Björn LU and Blom, Anna LU orcid (2004) In Journal of Biological Chemistry 279(23). p.23869-23873
Abstract
The phagocytosis of apoptotic cells is a complex process involving numerous interactions between the target cell and the macrophage. We have examined a role of the major soluble inhibitor of the classic and lectin complement pathways, C4b-binding protein (C4BP), in the clearance of apoptotic cells. The major form of C4BP present in blood is composed of seven alpha-chains and one beta-chain, which binds protein S ( PS). Approximately 70% of all PS in human plasma is trapped in such a complex and is able to localize C4BP to the surface of apoptotic cells due to the high affinity to phosphatidylserine. Free PS has recently been shown to enhance phagocytosis of apoptotic cells by macrophages. We observed a stimulatory effect of free PS on the... (More)
The phagocytosis of apoptotic cells is a complex process involving numerous interactions between the target cell and the macrophage. We have examined a role of the major soluble inhibitor of the classic and lectin complement pathways, C4b-binding protein (C4BP), in the clearance of apoptotic cells. The major form of C4BP present in blood is composed of seven alpha-chains and one beta-chain, which binds protein S ( PS). Approximately 70% of all PS in human plasma is trapped in such a complex and is able to localize C4BP to the surface of apoptotic cells due to the high affinity to phosphatidylserine. Free PS has recently been shown to enhance phagocytosis of apoptotic cells by macrophages. We observed a stimulatory effect of free PS on the engulfment of apoptotic cells (BL-41 and Jurkat) by primary human macrophages or THP-1 cells and a decrease of activity in serum depleted of PS in agreement with previous results. However, we also show that the process is strongly inhibited in the presence of the C4BP-PS complex. Addition of the C4BP-PS complex to serum deficient in both molecules abolished the enhancing effect of serum on phagocytosis. The effect of both free PS and the C4BP-PS complex could be inhibited with monoclonal antibody directed against the Gla domain of PS. Although the presence of the C4BP-PS complex on apoptotic cells may lead to decreased phagocytosis, it may still be beneficial to the host, since it could prevent secondary necrosis because it inhibits further complement attack. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
279
issue
23
pages
23869 - 23873
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • wos:000221702500006
  • scopus:2642533647
  • pmid:15096498
ISSN
1083-351X
DOI
10.1074/jbc.C400159200
language
English
LU publication?
yes
id
67db3123-ccc1-4f05-9bc4-5d16080b1080 (old id 122536)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15096498&dopt=Abstract
date added to LUP
2016-04-01 11:41:30
date last changed
2022-01-26 08:50:27
@article{67db3123-ccc1-4f05-9bc4-5d16080b1080,
  abstract     = {{The phagocytosis of apoptotic cells is a complex process involving numerous interactions between the target cell and the macrophage. We have examined a role of the major soluble inhibitor of the classic and lectin complement pathways, C4b-binding protein (C4BP), in the clearance of apoptotic cells. The major form of C4BP present in blood is composed of seven alpha-chains and one beta-chain, which binds protein S ( PS). Approximately 70% of all PS in human plasma is trapped in such a complex and is able to localize C4BP to the surface of apoptotic cells due to the high affinity to phosphatidylserine. Free PS has recently been shown to enhance phagocytosis of apoptotic cells by macrophages. We observed a stimulatory effect of free PS on the engulfment of apoptotic cells (BL-41 and Jurkat) by primary human macrophages or THP-1 cells and a decrease of activity in serum depleted of PS in agreement with previous results. However, we also show that the process is strongly inhibited in the presence of the C4BP-PS complex. Addition of the C4BP-PS complex to serum deficient in both molecules abolished the enhancing effect of serum on phagocytosis. The effect of both free PS and the C4BP-PS complex could be inhibited with monoclonal antibody directed against the Gla domain of PS. Although the presence of the C4BP-PS complex on apoptotic cells may lead to decreased phagocytosis, it may still be beneficial to the host, since it could prevent secondary necrosis because it inhibits further complement attack.}},
  author       = {{Kask, Lena and Trouw, Leendert and Dahlbäck, Björn and Blom, Anna}},
  issn         = {{1083-351X}},
  language     = {{eng}},
  number       = {{23}},
  pages        = {{23869--23873}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Biological Chemistry}},
  title        = {{The C4b-binding protein-protein S complex inhibits the phagocytosis of apoptotic cells.}},
  url          = {{http://dx.doi.org/10.1074/jbc.C400159200}},
  doi          = {{10.1074/jbc.C400159200}},
  volume       = {{279}},
  year         = {{2004}},
}