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Complement in removal of the dead – balancing inflammation

Martin, Myriam LU and Blom, Anna M. LU (2016) In Immunological Reviews 274(1). p.218-232
Abstract

Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances phagocytosis and thus ensures silent removal. Importantly, the process is tightly controlled by the binding of complement inhibitors C4b-binding protein and factor H, which attenuates late steps of complement activation and inflammation.... (More)

Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances phagocytosis and thus ensures silent removal. Importantly, the process is tightly controlled by the binding of complement inhibitors C4b-binding protein and factor H, which attenuates late steps of complement activation and inflammation. Furthermore, factor H becomes actively internalized by apoptotic cells, where it catalyzes the cleavage of intracellular C3 to C3b. The intracellularly derived C3b additionally opsonizes the cell surface further supporting safe and fast clearance and thereby aids to prevent autoimmunity. Internalized factor H also binds nucleosomes and directs monocytes into production of anti-inflammatory cytokines upon phagocytosis of such complexes. Disturbances in the complement-mediated clearance of dying cells result in persistence of autoantigens and development of autoimmune diseases like systemic lupus erythematosus, and may also be involved in development of age-related macula degeneration.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
apoptosis, clearance, complement system, factor H, intracellular complement, systemic lupus erythematosus
in
Immunological Reviews
volume
274
issue
1
pages
15 pages
publisher
Munksgaard International Publishers
external identifiers
  • scopus:84992449530
  • wos:000387059600015
ISSN
0105-2896
DOI
10.1111/imr.12462
language
English
LU publication?
yes
id
2d2c5141-c773-47e1-a56a-da89fe9c67f3
date added to LUP
2016-11-14 08:55:15
date last changed
2017-11-05 05:09:24
@article{2d2c5141-c773-47e1-a56a-da89fe9c67f3,
  abstract     = {<p>Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances phagocytosis and thus ensures silent removal. Importantly, the process is tightly controlled by the binding of complement inhibitors C4b-binding protein and factor H, which attenuates late steps of complement activation and inflammation. Furthermore, factor H becomes actively internalized by apoptotic cells, where it catalyzes the cleavage of intracellular C3 to C3b. The intracellularly derived C3b additionally opsonizes the cell surface further supporting safe and fast clearance and thereby aids to prevent autoimmunity. Internalized factor H also binds nucleosomes and directs monocytes into production of anti-inflammatory cytokines upon phagocytosis of such complexes. Disturbances in the complement-mediated clearance of dying cells result in persistence of autoantigens and development of autoimmune diseases like systemic lupus erythematosus, and may also be involved in development of age-related macula degeneration.</p>},
  author       = {Martin, Myriam and Blom, Anna M.},
  issn         = {0105-2896},
  keyword      = {apoptosis,clearance,complement system,factor H,intracellular complement,systemic lupus erythematosus},
  language     = {eng},
  month        = {11},
  number       = {1},
  pages        = {218--232},
  publisher    = {Munksgaard International Publishers},
  series       = {Immunological Reviews},
  title        = {Complement in removal of the dead – balancing inflammation},
  url          = {http://dx.doi.org/10.1111/imr.12462},
  volume       = {274},
  year         = {2016},
}