Advanced

Annexin A2 and A5 serve as new ligands for C1Q on apoptotic cells.

Martin, Myriam LU ; Leffler, Jonatan LU and Blom, Anna LU (2012) In Journal of Biological Chemistry 287(40). p.33733-33744
Abstract
C1q is the initiator of the classical complement pathway and opsonizes apoptotic cells to facilitate phagocytosis. Deficiency of C1q is the strongest known risk factor for development of systemic lupus erythematosus (SLE)a, which appears to be related to ensuing impaired clearance of apoptotic material. The objective of the current study was to investigate new ligands for C1q on the surface of apoptotic cells. We revealed that the two phospholipid-binding proteins annexin A2 and A5 are, beside DNA, significant C1q ligands. We furthermore demonstrated that C1q binds directly to histones exposed on the surface of dying cells but we did not detect significant interaction with phosphatidylserine. The complement inhibitors C4b-binding protein... (More)
C1q is the initiator of the classical complement pathway and opsonizes apoptotic cells to facilitate phagocytosis. Deficiency of C1q is the strongest known risk factor for development of systemic lupus erythematosus (SLE)a, which appears to be related to ensuing impaired clearance of apoptotic material. The objective of the current study was to investigate new ligands for C1q on the surface of apoptotic cells. We revealed that the two phospholipid-binding proteins annexin A2 and A5 are, beside DNA, significant C1q ligands. We furthermore demonstrated that C1q binds directly to histones exposed on the surface of dying cells but we did not detect significant interaction with phosphatidylserine. The complement inhibitors C4b-binding protein (C4BP) and factor H (FH) also interact with dying cells, most likely to decrease complement activation beyond the level of C3 in order to allow non-inflammatory clearance. Despite the fact that C4BP, FH and C1q share some ligands on dying cells, we showed that these three proteins did not compete with one another for binding to apoptotic cells. We additionally demonstrated that the way in which apoptosis is induced influenced both the degree of apoptosis and the binding of C1q. The knowledge, that annexin A2 and A5 act as ligands for C1q on apoptotic cells, sheds new light on the pathophysiology of autoimmune diseases. (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
Journal of Biological Chemistry
volume
287
issue
40
pages
33733 - 33744
publisher
ASBMB
external identifiers
  • wos:000309602100056
  • pmid:22879587
  • scopus:84866914816
ISSN
1083-351X
DOI
10.1074/jbc.M112.341339
language
English
LU publication?
yes
id
6bac779d-63d7-42ea-a45e-b20abea3c644 (old id 3047662)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22879587?dopt=Abstract
date added to LUP
2012-09-05 10:05:19
date last changed
2017-10-22 03:07:27
@article{6bac779d-63d7-42ea-a45e-b20abea3c644,
  abstract     = {C1q is the initiator of the classical complement pathway and opsonizes apoptotic cells to facilitate phagocytosis. Deficiency of C1q is the strongest known risk factor for development of systemic lupus erythematosus (SLE)a, which appears to be related to ensuing impaired clearance of apoptotic material. The objective of the current study was to investigate new ligands for C1q on the surface of apoptotic cells. We revealed that the two phospholipid-binding proteins annexin A2 and A5 are, beside DNA, significant C1q ligands. We furthermore demonstrated that C1q binds directly to histones exposed on the surface of dying cells but we did not detect significant interaction with phosphatidylserine. The complement inhibitors C4b-binding protein (C4BP) and factor H (FH) also interact with dying cells, most likely to decrease complement activation beyond the level of C3 in order to allow non-inflammatory clearance. Despite the fact that C4BP, FH and C1q share some ligands on dying cells, we showed that these three proteins did not compete with one another for binding to apoptotic cells. We additionally demonstrated that the way in which apoptosis is induced influenced both the degree of apoptosis and the binding of C1q. The knowledge, that annexin A2 and A5 act as ligands for C1q on apoptotic cells, sheds new light on the pathophysiology of autoimmune diseases.},
  author       = {Martin, Myriam and Leffler, Jonatan and Blom, Anna},
  issn         = {1083-351X},
  language     = {eng},
  number       = {40},
  pages        = {33733--33744},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Annexin A2 and A5 serve as new ligands for C1Q on apoptotic cells.},
  url          = {http://dx.doi.org/10.1074/jbc.M112.341339},
  volume       = {287},
  year         = {2012},
}