Advanced

Annexin-II, DNA and histones serve as Factor H ligands on the surface of apoptotic cells.

Leffler, Jonatan LU ; Herbert, Andrew P; Norström, Eva LU ; Schmidt, Chistoph Q; Barlow, Paul N; Blom, Anna LU and Martin, Myriam LU (2010) In Journal of Biological Chemistry 285(6). p.3766-3776
Abstract
Apoptotic cells are opsonized by complement components such as C1q and C3b, which increases their susceptibility to phagocytosis. Soluble complement inhibitors such as factor H (fH)b also recognise apoptotic cells to minimize the pro-inflammatory effects of downstream complement activation. We used four radiolabelled protein constructs that span different regions of the 20 CCP modules that make up fH, and found that fragments comprising CCPs 6-8, CCPs 8-15 and CCPs 19-20 but not CCPs 1-4, bound to apoptotic Jurkat T-cells. There are four possible ligand types on apoptotic cells that could recruit fH: proteins, carbohydrates, lipids and DNA. We found that CCPs 6-8 of fH bind to annexin-II, a trypsin-insensitive protein that becomes exposed... (More)
Apoptotic cells are opsonized by complement components such as C1q and C3b, which increases their susceptibility to phagocytosis. Soluble complement inhibitors such as factor H (fH)b also recognise apoptotic cells to minimize the pro-inflammatory effects of downstream complement activation. We used four radiolabelled protein constructs that span different regions of the 20 CCP modules that make up fH, and found that fragments comprising CCPs 6-8, CCPs 8-15 and CCPs 19-20 but not CCPs 1-4, bound to apoptotic Jurkat T-cells. There are four possible ligand types on apoptotic cells that could recruit fH: proteins, carbohydrates, lipids and DNA. We found that CCPs 6-8 of fH bind to annexin-II, a trypsin-insensitive protein that becomes exposed on surfaces of apoptotic cells. The second ligand of fH, which interacts with CCPs 6-8 and 19-20, is DNA. Confocal microscopy showed co-localisation of fH with antibodies specific for DNA. FH also binds to histones devoid of DNA and CCPs 1-4, 6-8 and 8-15 mediate this interaction. Treatment of apoptotic cells with neuraminidase, chondroitinase, heparitinase and heparinase did not change fH-binding. Treatment of apoptotic cells with phospholipase A2 dramatically increased both binding of fH and cell-surface DNA. We also excluded the possibility that fH interacts with lysophospholipids using surface plasmon resonance and flow cytometry with lipid-coated beads. Identification of annexin-II as one of the fH ligands on apoptotic cells together with the fact that autoantibodies against annexin-II are found in systemic lupus erythematosus provides further insight into understanding of the pathogenesis of this disease. (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
285
issue
6
pages
3766 - 3776
publisher
ASBMB
external identifiers
  • wos:000275254000029
  • pmid:19951950
  • scopus:77950499825
ISSN
1083-351X
DOI
10.1074/jbc.M109.045427
language
English
LU publication?
yes
id
9c199fac-7887-421a-9470-c4675ad30251 (old id 1524146)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19951950?dopt=Abstract
date added to LUP
2010-01-07 15:54:11
date last changed
2018-05-29 10:56:59
@article{9c199fac-7887-421a-9470-c4675ad30251,
  abstract     = {Apoptotic cells are opsonized by complement components such as C1q and C3b, which increases their susceptibility to phagocytosis. Soluble complement inhibitors such as factor H (fH)b also recognise apoptotic cells to minimize the pro-inflammatory effects of downstream complement activation. We used four radiolabelled protein constructs that span different regions of the 20 CCP modules that make up fH, and found that fragments comprising CCPs 6-8, CCPs 8-15 and CCPs 19-20 but not CCPs 1-4, bound to apoptotic Jurkat T-cells. There are four possible ligand types on apoptotic cells that could recruit fH: proteins, carbohydrates, lipids and DNA. We found that CCPs 6-8 of fH bind to annexin-II, a trypsin-insensitive protein that becomes exposed on surfaces of apoptotic cells. The second ligand of fH, which interacts with CCPs 6-8 and 19-20, is DNA. Confocal microscopy showed co-localisation of fH with antibodies specific for DNA. FH also binds to histones devoid of DNA and CCPs 1-4, 6-8 and 8-15 mediate this interaction. Treatment of apoptotic cells with neuraminidase, chondroitinase, heparitinase and heparinase did not change fH-binding. Treatment of apoptotic cells with phospholipase A2 dramatically increased both binding of fH and cell-surface DNA. We also excluded the possibility that fH interacts with lysophospholipids using surface plasmon resonance and flow cytometry with lipid-coated beads. Identification of annexin-II as one of the fH ligands on apoptotic cells together with the fact that autoantibodies against annexin-II are found in systemic lupus erythematosus provides further insight into understanding of the pathogenesis of this disease.},
  author       = {Leffler, Jonatan and Herbert, Andrew P and Norström, Eva and Schmidt, Chistoph Q and Barlow, Paul N and Blom, Anna and Martin, Myriam},
  issn         = {1083-351X},
  language     = {eng},
  number       = {6},
  pages        = {3766--3776},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Annexin-II, DNA and histones serve as Factor H ligands on the surface of apoptotic cells.},
  url          = {http://dx.doi.org/10.1074/jbc.M109.045427},
  volume       = {285},
  year         = {2010},
}