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Factor H binds to washed human platelets

Vaziri-Sani, F. LU ; Hellwage, J. ; Zipfel, P. F. ; Sjöholm, A. G. LU ; Iancu, R. LU and Karpman, D. LU orcid (2005) In Journal of Thrombosis and Haemostasis 3(1). p.154-162
Abstract

Background: Factor H regulates the alternative pathway of complement. The protein has three heparin-binding sites, is synthesized primarily in the liver and copurifies from platelets with thrombospondin-1. Factor H mutations at the C-terminus are associated with atypical hemolytic uremic syndrome, a condition in which platelets are consumed. Objectives The aim of this study was to investigate if factor H interacts with platelets. Methods: Binding of factor H, recombinant C- or N-terminus constructs and a C-terminus mutant to washed (plasma and complement-free) platelets was analyzed by flow cytometry. Binding of factor H and constructs to thrombospondin-1 was measured by surface plasmon resonance. Results: Factor H bound to platelets in... (More)

Background: Factor H regulates the alternative pathway of complement. The protein has three heparin-binding sites, is synthesized primarily in the liver and copurifies from platelets with thrombospondin-1. Factor H mutations at the C-terminus are associated with atypical hemolytic uremic syndrome, a condition in which platelets are consumed. Objectives The aim of this study was to investigate if factor H interacts with platelets. Methods: Binding of factor H, recombinant C- or N-terminus constructs and a C-terminus mutant to washed (plasma and complement-free) platelets was analyzed by flow cytometry. Binding of factor H and constructs to thrombospondin-1 was measured by surface plasmon resonance. Results: Factor H bound to platelets in a dose-dependent manner. The major binding site was localized to the C-terminus. The interaction was partially blocked by heparin. Inhibition with anti-GPIIb/IIIa, or with fibrinogen, suggested that the platelet GPIIb/IIIa receptor is involved in factor H binding. Factor H binds to thrombospondin-1. Addition of thrombospondin-1 increased factor H binding to platelets. Factor H mutated at the C-terminus also bound to platelets, albeit to a significantly lesser degree. Conclusions: This study reports a novel property of factor H, i.e. binding to platelets, either directly via the GPIIb/IIIa receptor or indirectly via thrombospondin-1, in the absence of complement. Binding to platelets was mostly mediated by the C-terminal region of factor H and factor H mutated at the C-terminus exhibited reduced binding.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Complement, Factor H, Hemolytic uremic syndrome, Platelets
in
Journal of Thrombosis and Haemostasis
volume
3
issue
1
pages
154 - 162
publisher
Wiley-Blackwell
external identifiers
  • pmid:15634279
  • scopus:20444447542
ISSN
1538-7933
DOI
10.1111/j.1538-7836.2004.01010.x
language
English
LU publication?
yes
id
0d7a14cf-4425-46a0-9f73-3b0da0481807
date added to LUP
2022-03-23 10:37:17
date last changed
2024-01-12 23:22:17
@article{0d7a14cf-4425-46a0-9f73-3b0da0481807,
  abstract     = {{<p>Background: Factor H regulates the alternative pathway of complement. The protein has three heparin-binding sites, is synthesized primarily in the liver and copurifies from platelets with thrombospondin-1. Factor H mutations at the C-terminus are associated with atypical hemolytic uremic syndrome, a condition in which platelets are consumed. Objectives The aim of this study was to investigate if factor H interacts with platelets. Methods: Binding of factor H, recombinant C- or N-terminus constructs and a C-terminus mutant to washed (plasma and complement-free) platelets was analyzed by flow cytometry. Binding of factor H and constructs to thrombospondin-1 was measured by surface plasmon resonance. Results: Factor H bound to platelets in a dose-dependent manner. The major binding site was localized to the C-terminus. The interaction was partially blocked by heparin. Inhibition with anti-GPIIb/IIIa, or with fibrinogen, suggested that the platelet GPIIb/IIIa receptor is involved in factor H binding. Factor H binds to thrombospondin-1. Addition of thrombospondin-1 increased factor H binding to platelets. Factor H mutated at the C-terminus also bound to platelets, albeit to a significantly lesser degree. Conclusions: This study reports a novel property of factor H, i.e. binding to platelets, either directly via the GPIIb/IIIa receptor or indirectly via thrombospondin-1, in the absence of complement. Binding to platelets was mostly mediated by the C-terminal region of factor H and factor H mutated at the C-terminus exhibited reduced binding.</p>}},
  author       = {{Vaziri-Sani, F. and Hellwage, J. and Zipfel, P. F. and Sjöholm, A. G. and Iancu, R. and Karpman, D.}},
  issn         = {{1538-7933}},
  keywords     = {{Complement; Factor H; Hemolytic uremic syndrome; Platelets}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{154--162}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Thrombosis and Haemostasis}},
  title        = {{Factor H binds to washed human platelets}},
  url          = {{http://dx.doi.org/10.1111/j.1538-7836.2004.01010.x}},
  doi          = {{10.1111/j.1538-7836.2004.01010.x}},
  volume       = {{3}},
  year         = {{2005}},
}