Thromb Haemost 2006; 96(03): 309-316
DOI: 10.1160/TH05-11-0729
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Recombinant factor VIII and factor VIII-von Willebrand factor complex do not present danger signals for human dendritic cells

Katharina Pfistershammer
1   BMT-Research, Vienna, Austria
2   Institute of Immunology, Medical University of Vienna, Vienna, Austria
,
Johannes Stöckl
1   BMT-Research, Vienna, Austria
2   Institute of Immunology, Medical University of Vienna, Vienna, Austria
,
Jürgen Siekmann
3   Baxter BioScience, Vienna, Austria
,
Peter L. Turecek
3   Baxter BioScience, Vienna, Austria
,
Hans Peter Schwarz
1   BMT-Research, Vienna, Austria
3   Baxter BioScience, Vienna, Austria
,
Birgit M. Reipert
1   BMT-Research, Vienna, Austria
3   Baxter BioScience, Vienna, Austria
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 08. November 2005

Accepted after resubmission 27. Juli 2006

Publikationsdatum:
30. November 2017 (online)

Summary

Several lines of evidence have shown that antibody responses to coagulation factor VIII (FVIII) in patients with hemophilia A depend on the help of activated CD4+ T cells. The primary activation of CD4+ T cells requires interaction with mature dendritic cells (DCs) that present antigenic peptides in the context of MHC class II and express costimulatory molecules. Maturation of DCs requires danger signals provided by exogenous or endogenous stimuli such as pathogen-derived products or inflammatory cytokines. We asked the question whether FVIII itself, FVIII complexed with von Willebrand factor (VWF) or thrombin-activated FVIII contain danger signals for human DCs that induce the upregulation of costimulatory molecules or the expression of proinflammatory cytokines necessary for effec tive activation of CD4+ T cells. Human peripheral monocytes were differentiated into DCs. FVIII, thrombin-activated FVIII, VWF, VWF-FVIII, lipopolysaccharide (LPS), LPS+FVIII, LPS+VWF or LPS+FVIII-VWF were added either on day 0 or on day 5 of differentiation cultures. Differentiation markers, cytokines in cell culture supernatants and the capacity of DCs to stimulate autologous and allogeneic T cells were analysed after seven days of differentiation cultures. Our results indicate that neither FVIII, thrombin-activated FVIII, VWF nor a complex of FVIII and VWF modulate the maturation of human DCs or their capacity to stimulate autologous or allogeneic T cells. We conclude that neither of these proteins present danger signals to human DCs.

 
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