Factor XIII improves platelet adhesion to fibrinogen by protein disulfide isomerase-mediated activity

Judith Lahav, Ariella Tvito, Zsuzsa Bagoly, Rima Dardik, Aida Inbal

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background Factor XIII (FXIII), a plasma pro-transglutaminase, consists of two A subunits and two B subunits (FXIIIA2B2). Following activation by thrombin, it cross-links fibrin chains at the final step of coagulation. We previously reported that FXIII subunit A (FXIIIA) serves as a protein disulfide isomerase (PDI), and that PDI promotes platelet adhesion and aggregation. Objective This study sought to examine possible mechanistic effect of FXIII on platelet adhesion to fibrinogen; specifically, the role of its PDI activity. Methods Ex vivo experiments: Blood platelets derived from five patients with hereditary FXIIIA deficiency before and after treatment with Fibrogammin-P (FXIIIA2B2 concentrate) were washed and incubated on immobilized fibrinogen. Bound platelets were stained and counted by microscopy. In vitro experiments: Platelets derived from patients before treatment and five healthy controls were washed and analyzed for adhesion in the presence or absence of Fibrogammin-P or recombinant FXIII (FXIIIA2 concentrate). Results In ex vivo experiments, one hour after Fibrogammin-P treatment, mean (± SEM) platelet adhesion to fibrinogen increased by 27 ± 2.32% (p < 0.001). In in vitro experiments, treatment with Fibrogammin-P or recombinant FXIII (10 IU/mL each) enhanced platelet adhesion to fibrinogen (in patients, by 29.95 ± 6.7% and 29.05 ± 5.3%, respectively; in controls, by 26.06 ± 3.24% and 26.91 ± 4.72, respectively; p < 0.04 for all). Iodoacetamide-treated FXIII (I-FXIII), where transglutaminase activity is blocked, showed similar enhanced adhesion as untreated FXIII. By contrast, addition of an antibody that specifically blocks FXIIIA-PDI activity inhibited FXIII-mediated platelet adhesion to fibrinogen by 65%. Conclusion These findings indicate that FXIII-induced enhancement of platelet adhesion is mediated by FXIII-PDI activity.

Original languageEnglish
Pages (from-to)338-341
Number of pages4
JournalThrombosis research
Volume131
Issue number4
DOIs
Publication statusPublished - Apr 1 2013

    Fingerprint

Keywords

  • Factor XIII
  • PDI
  • Transglutaminase
  • platelet adhesion

ASJC Scopus subject areas

  • Hematology

Cite this