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:
https://lup.lub.lu.se/record/3047662
- author
- Martin, Myriam
LU
; Leffler, Jonatan
LU
and Blom, Anna
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 287
- issue
- 40
- pages
- 33733 - 33744
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000309602100056
- pmid:22879587
- scopus:84866914816
- pmid:22879587
- 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
- 2016-04-01 10:06:23
- date last changed
- 2025-04-04 14:37:59
@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 = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Annexin A2 and A5 serve as new ligands for C1Q on apoptotic cells.}},
url = {{https://lup.lub.lu.se/search/files/1568078/3164685.pdf}},
doi = {{10.1074/jbc.M112.341339}},
volume = {{287}},
year = {{2012}},
}