scholarly journals No evidence for a direct effect of von Willebrand factor's ABH blood group antigens on von Willebrand factor clearance

2015 ◽  
Vol 13 (4) ◽  
pp. 592-600 ◽  
Author(s):  
D. J. Groeneveld ◽  
T. van Bekkum ◽  
K. L. Cheung ◽  
R. J. Dirven ◽  
G. Castaman ◽  
...  
Keyword(s):  
Blood Group ◽  
Direct Effect ◽  
Von Willebrand Factor ◽  
Blood Group Antigens ◽  
Abh Blood Group Antigens ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Human plasma alpha 2-macroglobulin and von Willebrand factor possess covalently linked ABO(H) blood group antigens in subjects with corresponding ABO phenotype

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 663-668
Author(s):  
T Matsui ◽  
Y Fujimura ◽  
S Nishida ◽  
K Titani
Keyword(s):  
Blood Group ◽  
Von Willebrand Factor ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Apparent Molecular Weight ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Group Antigens ◽  
Ulex Europaeus ◽  
Von Willebrand ◽  
Willebrand Factor

We recently identified ABO(H) blood group structures in Asn-linked sugar chains of human von Willebrand factor (vWF) purified from factor VIII concentrates (J Biol Chem 267:8723, 1992). We surveyed plasma glycoproteins carrying ABO(H) blood group antigens by Western blotting analysis and sandwich enzyme-linked immunosorbent assay using blood group-specific monoclonal antibodies (MoAbs) and a lectin. Two major plasma proteins showing apparent molecular weight of about 180 Kd and 270 Kd by sodium dodecyl sulfate polyacrylamide gel electrophoresis reacted with blood group-specific MoAbs and Ulex europaeus lectin I in accordance with donor blood group. Direct sequence analysis of the protein bands showed their identity with the N-terminal sequences of alpha 2-macroglobulin (alpha 2M) and vWF, respectively. The two bands also reacted with anti-alpha 2M and anti-vWF antibodies. The alpha 2M and vWF prepared from plasma by immunoprecipitation showed the appropriate blood group antigenicity. After incubation with endoglycosidase F, both alpha 2M and vWF lost almost all reactivity with anti-blood group reagents. About 90% of plasma vWF, but only approximately 10% of alpha 2M, was immunoprecipitated with anti-blood group antibody. These results indicate that at least two plasma glycoproteins, vWF and alpha 2M, possess Asn-linked ABO(H) blood group antigens in normal individuals with corresponding ABO phenotype. Therefore, ABO(H) blood group antigens in plasma glycoproteins should be considered during preparation of plasma materials for therapeutic use.

scholarly journals ABO blood group is a determinant of von Willebrand factor protein levels in human pulmonary endothelial cells

2019 ◽  
Vol 73 (6) ◽  
pp. 347-349 ◽  
Author(s):  
Glenn P Murray ◽  
Steven R Post ◽  
Ginell R Post
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Blood Group ◽  
Von Willebrand Factor ◽  
Blood Type ◽  
Abo Blood Group ◽  
Blood Group Antigens ◽  
Protein Levels ◽  
Von Willebrand ◽  
Willebrand Factor

ABO blood group antigens are expressed on von Willebrand factor (VWF) and glycosylation patterns influence circulating VWF levels. The aim of this study was to examine the effect of ABO blood type on tissue-associated VWF protein levels. We selected 35 formalin-fixed paraffin-embedded pulmonary tissue blocks obtained at autopsy from decedents who died from pulmonary embolism with known ABO blood groups (O, A, B and AB phenotypes), prepared tissue microarrays (TMAs) and stained TMAs with antibodies to VWF and platelet/endothelial cell adhesion marker-1 (PECAM-1) as a marker of endothelial cells. A pixel count scoring algorithm was used to quantify VWF and PECAM-1 staining intensity in pulmonary arterioles in digitised images. Compared with type O, non-O individuals have a significantly higher amount of endothelial cell-associated VWF protein expression. VWF protein levels associated with pulmonary vascular endothelial cells is influenced by ABO antigenic determinants.

Heterogeneous Detection of A-antigen on von Willebrand Factor Derived from Platelets, Endothelial Cells and Plasma

2002 ◽  
Vol 87 (06) ◽  
pp. 990-996 ◽  
Author(s):  
Peter Collins ◽  
Derrick Bowen ◽  
Simon Brown
Keyword(s):  
Endothelial Cells ◽  
Blood Group ◽  
Von Willebrand Factor ◽  
Saphenous Vein ◽  
Umbilical Vein ◽  
Abo Blood Group ◽  
Blood Group Antigens ◽  
Exact Function ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe exact function of the carbohydrate component of von Willebrand factor (VWF) is unknown. ABO blood group antigens are present as integral structures on the oligosaccharide side chains and it has long been recognised that ABO blood group is a determinant of VWF levels. The mechanism for this is not known. Using a monoclonal antibody against the A-antigen, we investigated the presence of this antigen on VWF from plasma, platelets, human umbilical vein endothelial cells (HUVEC) and saphenous vein endothelial cells. Initial studies on plasma VWF revealed that 23.5% of samples appeared to be negative for the A-antigen. This was shown to correlate with the A2 subtype of the A-antigen (p <0.01). Analysis of intracellular VWF from saphenous vein endothelial cells revealed low levels of A-antigen to be present in comparison to the corresponding plasma VWF. In contrast, VWF from platelets and HUVEC gave no detectable A-antigen. However, within 1 h of administration of DDAVP to type 1 VWD patients, there was a >2-fold increase in the A-antigen/VWF:Ag ratio for VWF in the plasma. In vitro experiments with serum N-acetlygalactosaminyltransferase failed to demonstrate any addition of A-antigen to platelet or HUVEC VWF. These data are consistent with heterogeneity in the content of A-antigen on VWF from different physiological compartments. Also, they are consistent with either a change in the A-antigen content of VWF after release from the intracellular compartment or a difference in the intracellular addition of A-antigen to VWF by endothelium from different vascular beds.

Specific N- and O-Linked Carbohydrate Structures Mediate Von Willebrand Factor Interaction with Galectins -1 and -3

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2234-2234 ◽  
Author(s):  
Orla Rawley ◽  
Jamie O'Sullivan ◽  
Gudmundur Bergsson ◽  
Alain Chan ◽  
Rachel Therese McGrath ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Blood Group ◽  
Von Willebrand Factor ◽  
Blood Group Antigens ◽  
Terminal Galactose ◽  
Pngase F ◽  
Galectin 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Abstract 2234 Von Willebrand Factor (VWF) is extensively glycosylated with both N- and O-linked carbohydrates. Moreover, these complex glycan structures influence VWF functional properties, including susceptibility to ADAMTS13 proteolysis, and plasma clearance. The molecular mechanisms through which VWF glycosylation (including ABO blood group antigens) act to influence VWF physiology remains unexplained. However, recent data suggest that VWF circulates in normal plasma bound to various carbohydrate-binding proteins, including specific members of the galectin family. In addition, galectin-3 binding has been reported to influence VWF cleavage by ADAMTS13. In this context, we sought to elucidate the role of specific VWF glycan determinants in modulating galectin interaction. VWF was purified from human plasma (pdVWF) by cryoprecipitation and gel filtration. VWF glycosylation was then modified using exoglycosidases and quantified by specific lectin ELISAs. Blood group specific VWF was also purified from pooled group AB, O, or Bombay plasmas. Galectins-1 and -3 were transiently expressed in competent E-coli cells with an N-terminal histidine tag, and purified by nickel chromatography. Finally, binding interactions were characterized via modified immunosorbant assay. In keeping with the previous report of Lenting et al, human pdVWF bound to both galectin-1 and galectin-3 in a dose-dependent manner. Enzymatic desialylation of pdVWF with α2-3,6,8,9 neuraminidase (Neu-VWF) markedly enhanced binding to galectin-1 (231±6%, p<0.0001). Similarly, removal of terminal sialic acid also increased binding to galectin-3, albeit to a lesser extent (136±6%, p<0.05). To further define the role of VWF glycans in regulating galectin binding, pdVWF was exposed to sequential neuraminidase and galactosidase digestions to remove terminal sialic acid and sub-terminal galactose residues (NeuGal-VWF). In contrast to the enhanced binding of Neu-VWF, binding of NeuGal-VWF to both galectin -1 and -3 was significantly reduced (51±5% and 52±6% compared to pdVWF; p<0.005). Cumulatively these findings suggest that loss of capping sialic acid and exposure of sub-terminal galactose critically regulates VWF-galectin binding. Treatment with PNGase F to completely remove N-linked carbohydrate structures (PNG-VWF) markedly decreased binding to galectin -1 and -3 (13±1% and 57±2%, p<0.001). Moreover, combined PNGase F and O-glycosidase digestions further attenuated galectin-3 binding (21±1%, p<0.001), suggesting that both the N- and O-linked glycans are involved in mediating the VWF-galectin interaction. ABO(H) blood group antigens are expressed on both the N-linked and O-linked glycans of human VWF. Moreover, ABO(H) determinants influence VWF susceptibility to ADAMTS13 proteolysis and plasma VWF half-life, through unknown mechanisms. Purified VWF from normal group AB individuals bound to both galectin-1 and galectin-3 significantly better than group O VWF (146±8% and 483±19%; p<0.01). Conversely, no significant difference in binding was observed between Group O and Bombay VWF. Consequently, although terminal A (GalNAc) and B (Gal) sugar moieties promote galectin binding, expression of terminal α1–2 fucose residues is not important. The glycosylation profile of platelet-VWF differs from that of pdVWF. In particular, platelet-VWF expresses reduced levels of both capping sialic acid and sub-terminal galactose residues (∼50%), and lacks AB blood group antigens. To characterize the effects of this differential sugar expression on galectin binding, platelet-derived VWF was isolated and purified (platelet freeze-thawing followed by immuno-affinity chromatography with monoclonal CLB-Rag20). In keeping with the reduction in Gal and AB blood group antigen expression, platelet VWF bound less well to galectin-1 and galectin-3 (72±6% and 67±7% versus pdVWF; p<0.05). These novel data demonstrate that both the N- and O-linked oligosaccharide structures of VWF are involved in mediating galectin binding. In particular, expression of terminal AB blood group antigens, and expression of sub-terminal galactose moieties following loss of capping sialic acid, both markedly enhance galectin binding affinity. Further studies will be required to define how galectin binding is involved in mediating the functional consequences of variation in VWF glycans. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Human plasma alpha 2-macroglobulin and von Willebrand factor possess covalently linked ABO(H) blood group antigens in subjects with corresponding ABO phenotype

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 663-668 ◽  
Author(s):  
T Matsui ◽  
Y Fujimura ◽  
S Nishida ◽  
K Titani
Keyword(s):  
Blood Group ◽  
Von Willebrand Factor ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Apparent Molecular Weight ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Group Antigens ◽  
Ulex Europaeus ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract We recently identified ABO(H) blood group structures in Asn-linked sugar chains of human von Willebrand factor (vWF) purified from factor VIII concentrates (J Biol Chem 267:8723, 1992). We surveyed plasma glycoproteins carrying ABO(H) blood group antigens by Western blotting analysis and sandwich enzyme-linked immunosorbent assay using blood group-specific monoclonal antibodies (MoAbs) and a lectin. Two major plasma proteins showing apparent molecular weight of about 180 Kd and 270 Kd by sodium dodecyl sulfate polyacrylamide gel electrophoresis reacted with blood group-specific MoAbs and Ulex europaeus lectin I in accordance with donor blood group. Direct sequence analysis of the protein bands showed their identity with the N-terminal sequences of alpha 2-macroglobulin (alpha 2M) and vWF, respectively. The two bands also reacted with anti-alpha 2M and anti-vWF antibodies. The alpha 2M and vWF prepared from plasma by immunoprecipitation showed the appropriate blood group antigenicity. After incubation with endoglycosidase F, both alpha 2M and vWF lost almost all reactivity with anti-blood group reagents. About 90% of plasma vWF, but only approximately 10% of alpha 2M, was immunoprecipitated with anti-blood group antibody. These results indicate that at least two plasma glycoproteins, vWF and alpha 2M, possess Asn-linked ABO(H) blood group antigens in normal individuals with corresponding ABO phenotype. Therefore, ABO(H) blood group antigens in plasma glycoproteins should be considered during preparation of plasma materials for therapeutic use.

scholarly journals Blood group alters platelet binding kinetics to von Willebrand factor and consequently platelet function

Blood ◽  
2019 ◽  
Vol 133 (12) ◽  
pp. 1371-1377 ◽  
Author(s):  
Eimear Dunne ◽  
Qin M. Qi ◽  
Eric S. Shaqfeh ◽  
Jamie M. O’Sullivan ◽  
Ingmar Schoen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Blood Group ◽  
Platelet Function ◽  
Von Willebrand Factor ◽  
Critical Role ◽  
Blood Type ◽  
Blood Group Antigens ◽  
Interaction Modeling ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Blood type O is associated with a lower risk of myocardial infarction. Platelets play a critical role in myocardial infarction. It is not known whether the expression of blood group antigens on platelet proteins alters platelet function; we hypothesized that platelet function would be different between donors with blood type O and those with non-O. To address this hypothesis, we perfused blood from healthy type O donors (n = 33) or non-O donors (n = 54) over pooled plasma derived von Willebrand factor (VWF) protein and purified blood type–specific VWF at arterial shear and measured platelet translocation dynamics. We demonstrate for the first time that type O platelets travel farther at greater speeds before forming stable bonds with VWF. To further characterize these findings, we used a novel analytical model of platelet interaction. Modeling revealed that the kinetics for GPIb/VWF binding rate are significantly lower for type O compared with non-O platelets. Our results demonstrate that platelets from type O donors interact less with VWF at arterial shear than non-O platelets. Our results suggest a potential mechanism for the reduced risk of myocardial infarction associated with blood type O.

Effects of plasma glycosyltransferase on the ABO(H) blood group antigens of human von Willebrand factor

2018 ◽  
Vol 108 (2) ◽  
pp. 139-144 ◽  
Author(s):  
Taiki Kano ◽  
Kazunao Kondo ◽  
Jiharu Hamako ◽  
Fumio Matsushita ◽  
Kazuya Sakai ◽  
...  
Keyword(s):  
Blood Group ◽  
Von Willebrand Factor ◽  
Blood Group Antigens ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Role of A and B blood group antigens in the expression of adhesive activity of von Willebrand factor

2000 ◽  
Vol 109 (4) ◽  
pp. 857-864 ◽  
Author(s):  
Ravindra Sarode ◽  
Jack Goldstein ◽  
Ira I. Sussman ◽  
Ronald L. Nagel ◽  
Han-Mou Tsai
Keyword(s):  
Blood Group ◽  
Von Willebrand Factor ◽  
Blood Group Antigens ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
B Blood Group
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