Factor H binds to washed human platelets
(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.
(Less)
- author
- Vaziri-Sani, F. LU ; Hellwage, J. ; Zipfel, P. F. ; Sjöholm, A. G. LU ; Iancu, R. LU and Karpman, D. LU
- organization
- publishing date
- 2005-01
- 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}}, }