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Interactions of histidine-rich glycoprotein with immunoglobulins and proteins of the complement system.

Manderson, Gavin LU ; Martin, M; Önnerfjord, Patrik LU ; Saxne, Tore LU ; Schmidtchen, Artur LU ; Mollnes, T E; Heinegård, Dick LU and Blom, A M (2009) In Molecular Immunology Aug 10. p.3388-3398
Abstract
This study describes how the serum protein histidine-rich glycoprotein (HRG) affects the complement system. We show that HRG binds strongly to several complement proteins: C1q, factor H and C4b-binding protein and that it is found complexed with these proteins in human sera and synovial fluids of rheumatoid arthritis patients. HRG also binds C8 and to a lesser extent mannose-binding lectin, C4 and C3. However, HRG alone neither activates nor inhibits complement. Both HRG and C1q bind to necrotic cells and increase their phagocytosis. We found that C1q competes weakly with HRG for binding to necrotic cells whilst HRG does not compete with C1q. Furthermore, HRG enhances complement activation on necrotic cells measured as deposition of C3b.... (More)
This study describes how the serum protein histidine-rich glycoprotein (HRG) affects the complement system. We show that HRG binds strongly to several complement proteins: C1q, factor H and C4b-binding protein and that it is found complexed with these proteins in human sera and synovial fluids of rheumatoid arthritis patients. HRG also binds C8 and to a lesser extent mannose-binding lectin, C4 and C3. However, HRG alone neither activates nor inhibits complement. Both HRG and C1q bind to necrotic cells and increase their phagocytosis. We found that C1q competes weakly with HRG for binding to necrotic cells whilst HRG does not compete with C1q. Furthermore, HRG enhances complement activation on necrotic cells measured as deposition of C3b. We show that HRG inhibits the formation of immune complexes of ovalbumin/anti-ovalbumin, whilst the reverse holds for C1q. Immune complexes formed in the presence of HRG show enhanced complement activation, whilst those formed in the presence of C1q show diminished complement activation. Taken together, HRG may assist in the maintenance of normal immune function by mediating the clearance of necrotic material, inhibiting the formation of insoluble immune complexes and enhancing their ability to activate complement, resulting in faster clearance. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Immunology
volume
Aug 10
pages
3388 - 3398
publisher
Pergamon
external identifiers
  • WOS:000271175000025
  • PMID:19674792
  • Scopus:70349564335
ISSN
1872-9142
DOI
10.1016/j.molimm.2009.07.011
language
English
LU publication?
yes
id
43ac3a01-5e2d-420a-b1ea-6278860823b1 (old id 1469792)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19674792?dopt=Abstract
date added to LUP
2009-09-07 16:01:27
date last changed
2016-10-13 04:28:13
@misc{43ac3a01-5e2d-420a-b1ea-6278860823b1,
  abstract     = {This study describes how the serum protein histidine-rich glycoprotein (HRG) affects the complement system. We show that HRG binds strongly to several complement proteins: C1q, factor H and C4b-binding protein and that it is found complexed with these proteins in human sera and synovial fluids of rheumatoid arthritis patients. HRG also binds C8 and to a lesser extent mannose-binding lectin, C4 and C3. However, HRG alone neither activates nor inhibits complement. Both HRG and C1q bind to necrotic cells and increase their phagocytosis. We found that C1q competes weakly with HRG for binding to necrotic cells whilst HRG does not compete with C1q. Furthermore, HRG enhances complement activation on necrotic cells measured as deposition of C3b. We show that HRG inhibits the formation of immune complexes of ovalbumin/anti-ovalbumin, whilst the reverse holds for C1q. Immune complexes formed in the presence of HRG show enhanced complement activation, whilst those formed in the presence of C1q show diminished complement activation. Taken together, HRG may assist in the maintenance of normal immune function by mediating the clearance of necrotic material, inhibiting the formation of insoluble immune complexes and enhancing their ability to activate complement, resulting in faster clearance.},
  author       = {Manderson, Gavin and Martin, M and Önnerfjord, Patrik and Saxne, Tore and Schmidtchen, Artur and Mollnes, T E and Heinegård, Dick and Blom, A M},
  issn         = {1872-9142},
  language     = {eng},
  pages        = {3388--3398},
  publisher    = {ARRAY(0x915d2b0)},
  series       = {Molecular Immunology},
  title        = {Interactions of histidine-rich glycoprotein with immunoglobulins and proteins of the complement system.},
  url          = {http://dx.doi.org/10.1016/j.molimm.2009.07.011},
  volume       = {Aug 10},
  year         = {2009},
}