The C4b-binding protein-protein S complex inhibits the phagocytosis of apoptotic cells.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/122536
- author
- Kask, Lena LU ; Trouw, Leendert LU ; Dahlbäck, Björn LU and Blom, Anna LU
- organization
- publishing date
- 2004
- 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}}, }