Type

Journal Article

Authors

James S O'Donnell
Teresa M Brophy
Roger J S Preston
Richard O'Kennedy
Barry Byrne
Michelle Lavin
Alain Chion
Kristina Gegenbauer
Orla Rawley
P Vince Jenkins
and 1 others

Subjects

Biochemistry

Topics
factor viii von willebrand factor factor 3 cell lines galectin 1 surface plasmon resonance galectin 3 high affinity

Galectin-1 and Galectin-3 Constitute Novel-Binding Partners for Factor VIII. (2015)

Abstract Recent studies have demonstrated that galectin-1 (Gal-1) and galectin-3 (Gal-3) can bind von Willebrand factor and directly modulate von Willebrand factor-dependent early thrombus formation in vivo. Because the glycans expressed on human factor VIII (FVIII) are similar to those of von Willebrand factor, we investigated whether galectins might also bind and modulate the activity of FVIII. Immunosorbant assays and surface plasmon resonance analysis confirmed that Gal-1 and Gal-3 bound purified FVIII with high affinity. Exoglycosidase removal of FVIII N-linked glycans significantly reduced binding to both Gal-1 and Gal-3. Moreover, combined removal of both the N- and O-glycans of FVIII further attenuated Gal-3 binding. Notably, specific digestion of FVIII high-mannose glycans at N239 and N2118 significantly impaired FVIII affinity for Gal-1. Importantly Gal-1, but not Gal-3, bound to free FVIII in the plasma milieu, and significantly inhibited FVIII functional activity. Interestingly, commercial recombinant FVIII (rFVIII) concentrates are manufactured in different cell lines and differ in their glycosylation profiles. Although the biological mechanism has not been defined, recent studies in previously untreated patients with severe hemophilia A reported significant differences in inhibitor development associated with different rFVIII products. Interestingly, Gal-1 and Gal-3 both displayed enhanced affinity for BHK-rFVIII compared with CHO-rFVIII. Furthermore, binding of Gal-1 and Gal-3 to BDD-FVIII was markedly reduced compared with full-length rFVIII. We have identified Gal-1 and Gal-3 as novel-binding partners for human FVIII and demonstrated that Gal-1 binding can influence the procoagulant activity of FVIII.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

James S O'Donnell, Teresa M Brophy, Roger J S Preston, Richard O'Kennedy, Barry Byrne, Michelle Lavin, Alain Chion, Kristina Gegenbauer, Orla Rawley, P Vince Jenkins and 1 others

Experts in our system

1
James S O'Donnell
Trinity College Dublin
Total Publications: 57
 
2
Teresa M Brophy
Royal College of Surgeons in Ireland
Total Publications: 8
 
3
Roger J S Preston
Trinity College Dublin
Total Publications: 32
 
4
R O'Kennedy
Dublin City University
Total Publications: 197
 
5
Barry Byrne
Dublin City University
Total Publications: 15
 
6
M Lavin
Royal College of Surgeons in Ireland
Total Publications: 9
 
7
Alain Chion
Royal College of Surgeons in Ireland
Total Publications: 7
 
8
Orla Rawley
Trinity College Dublin
Total Publications: 6
 
9
P Vince Jenkins
Trinity College Dublin
Total Publications: 8