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C4b-binding protein and factor h compensate for the loss of membrane-bound complement inhibitors to protect apoptotic cells against excessive complement attack

Trouw, Leendert LU ; Bengtsson, Anders LU ; Gelderman, Kyra LU ; Dahlbäck, Björn LU ; Sturfelt, Gunnar LU and Blom, Anna LU (2007) In Journal of Biological Chemistry 282(39). p.28540-28548
Abstract
Apoptotic cells have been reported to down- regulate membrane-bound complement regulatory proteins ( m- C- Reg) and to activate complement. Nonetheless, most apoptotic cells do not undergo complement- mediated lysis. Therefore, we hypothesized that fluid phase complement inhibitors would bind to apoptotic cells and compensate functionally for the loss of m- C- Reg. We observed that m- C- Reg are down- regulated rapidly upon apoptosis but that complement activation follows only after a gap of several hours. Coinciding with, but independent from, complement activation, fluid phase complement inhibitors C4b- binding protein ( C4BP) and factorH( fH) bind to the cells. C4BP and fH do not entirely prevent complement activation but strongly limit... (More)
Apoptotic cells have been reported to down- regulate membrane-bound complement regulatory proteins ( m- C- Reg) and to activate complement. Nonetheless, most apoptotic cells do not undergo complement- mediated lysis. Therefore, we hypothesized that fluid phase complement inhibitors would bind to apoptotic cells and compensate functionally for the loss of m- C- Reg. We observed that m- C- Reg are down- regulated rapidly upon apoptosis but that complement activation follows only after a gap of several hours. Coinciding with, but independent from, complement activation, fluid phase complement inhibitors C4b- binding protein ( C4BP) and factorH( fH) bind to the cells. C4BP and fH do not entirely prevent complement activation but strongly limit C3 and C9 deposition. Late apoptotic cells, present in blood of healthy controls and systemic lupus erythematosus patients, are also positive for C4BP and fH. Upon culture, the percentage of late apoptotic cells increases, paralleled by increased C4BP binding. C4BP binds to dead cells mainly via phosphatidylserine, whereas fH binds via multiple interactions with CRP playing no major role for binding of C4BP or fH. In conclusion, during late apoptosis, cells acquire fluid phase complement inhibitors that compensate for the downregulation of m- C- Reg and protect against excessive complement activation and lysis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
282
issue
39
pages
28540 - 28548
publisher
ASBMB
external identifiers
  • wos:000249642100028
  • scopus:35348980673
ISSN
1083-351X
DOI
10.1074/jbc.M704354200
language
English
LU publication?
yes
id
3d772f28-3944-4e38-a792-1c52d5c62ae6 (old id 656580)
date added to LUP
2008-08-13 16:12:41
date last changed
2017-10-22 03:49:58
@article{3d772f28-3944-4e38-a792-1c52d5c62ae6,
  abstract     = {Apoptotic cells have been reported to down- regulate membrane-bound complement regulatory proteins ( m- C- Reg) and to activate complement. Nonetheless, most apoptotic cells do not undergo complement- mediated lysis. Therefore, we hypothesized that fluid phase complement inhibitors would bind to apoptotic cells and compensate functionally for the loss of m- C- Reg. We observed that m- C- Reg are down- regulated rapidly upon apoptosis but that complement activation follows only after a gap of several hours. Coinciding with, but independent from, complement activation, fluid phase complement inhibitors C4b- binding protein ( C4BP) and factorH( fH) bind to the cells. C4BP and fH do not entirely prevent complement activation but strongly limit C3 and C9 deposition. Late apoptotic cells, present in blood of healthy controls and systemic lupus erythematosus patients, are also positive for C4BP and fH. Upon culture, the percentage of late apoptotic cells increases, paralleled by increased C4BP binding. C4BP binds to dead cells mainly via phosphatidylserine, whereas fH binds via multiple interactions with CRP playing no major role for binding of C4BP or fH. In conclusion, during late apoptosis, cells acquire fluid phase complement inhibitors that compensate for the downregulation of m- C- Reg and protect against excessive complement activation and lysis.},
  author       = {Trouw, Leendert and Bengtsson, Anders and Gelderman, Kyra and Dahlbäck, Björn and Sturfelt, Gunnar and Blom, Anna},
  issn         = {1083-351X},
  language     = {eng},
  number       = {39},
  pages        = {28540--28548},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {C4b-binding protein and factor h compensate for the loss of membrane-bound complement inhibitors to protect apoptotic cells against excessive complement attack},
  url          = {http://dx.doi.org/10.1074/jbc.M704354200},
  volume       = {282},
  year         = {2007},
}