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Role of complement and complement regulators in the removal of apoptotic cells

Trouw, Leendert LU ; Blom, Anna LU and Gasque, P (2008) In Molecular Immunology 45(5). p.1199-1207
Abstract
Apoptosis, followed by rapid phagocytic clearance, is the primary mechanism by which organisms dispose of unwanted cells. The intracellular and extracellular composition of an apoptotic cell changes to decrease immunogenicity and enhance its uptake. By changing their extracellular composition, apoptotic cells acquire the capacity to bind complement initiation molecules such as C1q and MBL. Binding of these molecules can lead to complement activation. Membrane bound complement inhibitors are down-regulated during apoptosis, which would leave the cell less protected against complement activation; however, recent data show that fluid-phase complement inhibitors may compensate for this loss of regulation. Importantly, binding of complement is... (More)
Apoptosis, followed by rapid phagocytic clearance, is the primary mechanism by which organisms dispose of unwanted cells. The intracellular and extracellular composition of an apoptotic cell changes to decrease immunogenicity and enhance its uptake. By changing their extracellular composition, apoptotic cells acquire the capacity to bind complement initiation molecules such as C1q and MBL. Binding of these molecules can lead to complement activation. Membrane bound complement inhibitors are down-regulated during apoptosis, which would leave the cell less protected against complement activation; however, recent data show that fluid-phase complement inhibitors may compensate for this loss of regulation. Importantly, binding of complement is a process that mainly takes place during the late stages of apoptosis. Most cells will be cleared before that stage under steady state conditions, but during overwhelming apoptosis or impaired phagocytosis, apoptotic cells may remain in tissues for a longer time and acquire complement proteins. Based on the data from deficiencies of early complement components and the development of systemic lupus erythematosus with accumulation of dead cells, it is clear that, under certain conditions, apoptotic cells persist, becoming necrotic and overloading the scavenging capacities of the complement system. Although the complement system is also involved in inducing apoptosis in target cells, this review will focus on the role of complement in the clearance of apoptotic cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Complement, Phagocytosis, Autoimmunity, SAMP, Apoptosis
in
Molecular Immunology
volume
45
issue
5
pages
1199 - 1207
publisher
Pergamon
external identifiers
  • pmid:17961651
  • wos:000253030000001
  • scopus:37349079469
ISSN
1872-9142
DOI
10.1016/j.molimm.2007.09.008
language
English
LU publication?
yes
id
690ff888-cd2c-46e1-9b37-f320f3f896da (old id 1138704)
date added to LUP
2008-04-29 09:17:55
date last changed
2017-10-01 04:00:32
@article{690ff888-cd2c-46e1-9b37-f320f3f896da,
  abstract     = {Apoptosis, followed by rapid phagocytic clearance, is the primary mechanism by which organisms dispose of unwanted cells. The intracellular and extracellular composition of an apoptotic cell changes to decrease immunogenicity and enhance its uptake. By changing their extracellular composition, apoptotic cells acquire the capacity to bind complement initiation molecules such as C1q and MBL. Binding of these molecules can lead to complement activation. Membrane bound complement inhibitors are down-regulated during apoptosis, which would leave the cell less protected against complement activation; however, recent data show that fluid-phase complement inhibitors may compensate for this loss of regulation. Importantly, binding of complement is a process that mainly takes place during the late stages of apoptosis. Most cells will be cleared before that stage under steady state conditions, but during overwhelming apoptosis or impaired phagocytosis, apoptotic cells may remain in tissues for a longer time and acquire complement proteins. Based on the data from deficiencies of early complement components and the development of systemic lupus erythematosus with accumulation of dead cells, it is clear that, under certain conditions, apoptotic cells persist, becoming necrotic and overloading the scavenging capacities of the complement system. Although the complement system is also involved in inducing apoptosis in target cells, this review will focus on the role of complement in the clearance of apoptotic cells.},
  author       = {Trouw, Leendert and Blom, Anna and Gasque, P},
  issn         = {1872-9142},
  keyword      = {Complement,Phagocytosis,Autoimmunity,SAMP,Apoptosis},
  language     = {eng},
  number       = {5},
  pages        = {1199--1207},
  publisher    = {Pergamon},
  series       = {Molecular Immunology},
  title        = {Role of complement and complement regulators in the removal of apoptotic cells},
  url          = {http://dx.doi.org/10.1016/j.molimm.2007.09.008},
  volume       = {45},
  year         = {2008},
}