Factor H binds to washed human platelets

Fariba Vaziri-Sani, J Hellwage, P F Zipfel, A G Sjoholm, R Iancu, D Karpman

Forskningsoutput: TidskriftsbidragArtikelPeer review

40 Citeringar (Scopus)

Sammanfattning

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 G 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.

OriginalspråkEngelska
Sidor (från-till)154-162
Antal sidor8
TidskriftJournal of Thrombosis and Haemostasis
Volym3
Utgåva1
DOI
StatusPublicerad - 2005
Externt publiceradJa

Nationell ämneskategori

  • Cell- och molekylärbiologi (30108)

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