Advanced

Complement classical pathway components are all important in clearance of apoptotic and secondary necrotic cells.

Gullstrand, Birgitta LU ; Mårtensson, Ulla LU ; Sturfelt, Gunnar LU ; Bengtsson, A A and Truedsson, Lennart LU (2009) In Clinical and Experimental Immunology 156. p.303-311
Abstract
Summary Inherited deficiencies in components of the classical complement pathway are strong disease susceptibility factors for the development of systemic lupus erythematosus (SLE) and there is a hierarchy among deficiency states, the strongest association being with C1q deficiency. We investigated the relative importance of the different complement pathways regarding clearance of apoptotic cells. Phagocytosis of labelled apoptotic Jurkat cells by monocyte-derived macrophages in the presence of sera from individuals with complement deficiencies was studied, as well as C3 deposition on apoptotic cells using flow cytometry. Sera from individuals deficient in C1q, C4, C2 or C3 all showed decreased phagocytosis. Mannose binding lectin (MBL)... (More)
Summary Inherited deficiencies in components of the classical complement pathway are strong disease susceptibility factors for the development of systemic lupus erythematosus (SLE) and there is a hierarchy among deficiency states, the strongest association being with C1q deficiency. We investigated the relative importance of the different complement pathways regarding clearance of apoptotic cells. Phagocytosis of labelled apoptotic Jurkat cells by monocyte-derived macrophages in the presence of sera from individuals with complement deficiencies was studied, as well as C3 deposition on apoptotic cells using flow cytometry. Sera from individuals deficient in C1q, C4, C2 or C3 all showed decreased phagocytosis. Mannose binding lectin (MBL) and the alternative pathway did not influence phagocytosis. Notably, the components of the complement classical pathway, including C1q, were equally important in clearance of apoptotic cells. This indicates that deposition of C3 fragments is of major significance; we therefore studied C3 deposition on apoptotic cells. Experiments with MBL-deficient serum depleted of C1q or factor D confirmed the predominance of the classical pathway. At low dilution, sera deficient of C1q, C4 or C2 supported C3 fragment deposition demonstrating alternative pathway activation. In conclusion, we have found that complement-mediated opsonization and phagocytosis of apoptotic cells, particularly those undergoing secondary necrosis, are dependent mainly upon an intact classical pathway. The alternative pathway is less important, but may play a role in some conditions. C1q was not more important than other classical pathway components, suggesting a role in additional pathogenetic processes in SLE other than clearance of apoptotic cells. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Experimental Immunology
volume
156
pages
303 - 311
publisher
British Society for Immunology
external identifiers
  • wos:000265032400018
  • pmid:19302245
  • scopus:64649093433
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2009.03896.x
language
English
LU publication?
yes
id
b6171f6a-3854-4a7a-89f7-a0d3ddfa71e6 (old id 1367591)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19302245?dopt=Abstract
date added to LUP
2009-04-07 15:18:41
date last changed
2017-03-26 04:28:04
@article{b6171f6a-3854-4a7a-89f7-a0d3ddfa71e6,
  abstract     = {Summary Inherited deficiencies in components of the classical complement pathway are strong disease susceptibility factors for the development of systemic lupus erythematosus (SLE) and there is a hierarchy among deficiency states, the strongest association being with C1q deficiency. We investigated the relative importance of the different complement pathways regarding clearance of apoptotic cells. Phagocytosis of labelled apoptotic Jurkat cells by monocyte-derived macrophages in the presence of sera from individuals with complement deficiencies was studied, as well as C3 deposition on apoptotic cells using flow cytometry. Sera from individuals deficient in C1q, C4, C2 or C3 all showed decreased phagocytosis. Mannose binding lectin (MBL) and the alternative pathway did not influence phagocytosis. Notably, the components of the complement classical pathway, including C1q, were equally important in clearance of apoptotic cells. This indicates that deposition of C3 fragments is of major significance; we therefore studied C3 deposition on apoptotic cells. Experiments with MBL-deficient serum depleted of C1q or factor D confirmed the predominance of the classical pathway. At low dilution, sera deficient of C1q, C4 or C2 supported C3 fragment deposition demonstrating alternative pathway activation. In conclusion, we have found that complement-mediated opsonization and phagocytosis of apoptotic cells, particularly those undergoing secondary necrosis, are dependent mainly upon an intact classical pathway. The alternative pathway is less important, but may play a role in some conditions. C1q was not more important than other classical pathway components, suggesting a role in additional pathogenetic processes in SLE other than clearance of apoptotic cells.},
  author       = {Gullstrand, Birgitta and Mårtensson, Ulla and Sturfelt, Gunnar and Bengtsson, A A and Truedsson, Lennart},
  issn         = {0009-9104},
  language     = {eng},
  pages        = {303--311},
  publisher    = {British Society for Immunology},
  series       = {Clinical and Experimental Immunology},
  title        = {Complement classical pathway components are all important in clearance of apoptotic and secondary necrotic cells.},
  url          = {http://dx.doi.org/10.1111/j.1365-2249.2009.03896.x},
  volume       = {156},
  year         = {2009},
}