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

Simon A. Brown; Peter W. Collins; Derrick J. Bowen

doi:10.1055/s-0037-1613123

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 87(06): 990-996
DOI: 10.1055/s-0037-1613123

Review Article

Schattauer GmbH

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

Simon A. Brown

¹Department of Haematology, University of Wales College of Medicine, Cardiff, Wales, UK

,

Peter W. Collins

¹Department of Haematology, University of Wales College of Medicine, Cardiff, Wales, UK

,

Derrick J. Bowen

¹Department of Haematology, University of Wales College of Medicine, Cardiff, Wales, UK

› Author Affiliations

Abstract

Summary

The 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.

Keywords

von Willebrand factor - ABO blood group - platelet - endothelial cell - DDAVP

Full Text

References

References
1 Hoyer LW, Shainoff JR. Factor VIII-related protein circulates in normal human plasma as high molecular weight multimers. Blood 1980; 55: 1056-9.
2 Bolhuis PA, Sakariassen KS, Sander HJ, Bouma BN, Sixma JJ. Binding of factor VIII-von Willebrand factor to human arterial subendothelium precedes increased platelet adhesion and enhances platelet spreading. J Lab Clin Med 1981; 97: 568-76.
3 Nachman R, Levin R, Jaffe EA. Synthesis of FVIII-related antigen by cultured guinea-pig megakaryocytes. J Clin Invest 1977; 60: 914-21.
4 Jaffe EA, Hoyer LW, Nachman RL. Synthesis of von Willebrand factor by cultured human endothelial cells. Proc Natl Acad Sci USA 1974; 71: 1906-9.
5 Wagner DD, Olmstead JB, Marder VJ. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol 1982; 95: 355-60.
6 Titani K, Kumar S, Takio K, Ericsson LH, Wade RD, Ashida K, Walsh KA, Michael WC, Evan JSadler, Fujikawa K. Amino acid sequence of human von Willebrand factor. Biochemistry 1986; 25: 3171-84.
7 Debeire T, Montreuil J, Samor B, Mazurier C, Goudemand M, Van Halbeek H, Vliegenthart JFG. Structure determination of the major asparagine-linked sugar chain of human factor VIII-von Willebrand factor. FEBS Lett 1983; 151: 22-6.
8 Samor B, Michalski J-C, Debray H, Mazurier C, Goudemand M, Van Halbeek H, Vliegenthart JFG, Montreuil J. Primary structure of a new tetraantennary glycan of the N-acetyllactosaminic type isolated from human factor VIII/von Willebrand factor. Eur J Biochem 1986; 158: 295-8.
9 Samor B, Michalski J-C, Mazurier C, Goudemand M, De Waard P, Vliegenthart JFG, Strecker G, Montreuil J. Primary structure of the major O-glycosidically linked carbohydrate unit of human von Willebrand factor. Glycoconj J 1989; 06: 263-70.
10 Matsui T, Titani K, Mizuochi T. Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. Occurrence of blood group A, B, and H(O) structures. J Biol Chem 1992; 267: 8723-31.
11 Sodetz JM, Paulson JC, McKee PA. Carbohydrate composition and identification of blood group A, B and H oligosaccharide structures on human factor VIII/von Willebrand factor. J Biol Chem 1979; 254: 10754-60.
12 Federici AB, Elder JH, De Marco L, Ruggeri ZM, Zimmerman TS. Carbohydrate moiety of von Willebrand factor is not necessary for maintaining multimeric structure and ristocetin cofactor activity but protects from proteolytic degradation. J Clin Invest 1984; 74: 2049-55.
13 Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69: 1691-5.
14 Reid ME, Lomas-Francis C. ABO blood group system. In: The blood group antigen facts book. Reid ME, Lomas-Francis C. London: Academic Press; 1997: 19-26.
15 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745-56.
16 Dacie JM, Lewis SM. Laboratory aspects of blood transfusion. In: Practical Haematology. (8th edition).. Dacie JM, Lewis SM. London: Churchill Livingstone; 1995: 137-8.
17 Gralnick HR, Williams SB, McKeown LP, Maisonneuve P, Jenneau C, Sultan Y, Rick ME. In vitro correction of the abnormal multimeric structure of von Willebrand factor in type IIa von Willebrand’s disease. Proc Natl Acad Sci USA 1985; 82: 5968-72.
18 Short PE, Williams CE, Picken AM, Hill FG. Factor VIII related antigen: an improved enzyme immunoassay. Med Lab Sci 1982; 39: 351-5.
19 Meyer D, Obert B, Pietu G, Lavergne JM, Zimmerman TS. Multimeric structure of factor VIII/von Willebrand factor in von Willebrand’s disease. J Lab Clin Med 1980; 95: 590-602.
20 Miller MA, Palascak JE, Thompson MR, Martelo NP. A modified SDS agarose gel method for determining factor VIII von Willebrand factor multimers using commercially available reagents. Thromb Res 1983; 39: 777-80.
21 Cartron JP, Gerbal A, Badet J, Ropars C, Salmon C. Assay of α-N-acetylgalactosaminyltransferases in human sera. Further evidence for several types of Am individuals. Vox Sang 1975; 28: 347-65.
22 Waters AH. Red cell cytochemistry. In: Practical Haematology. (8th edition).. Dacie JM, Lewis SM. London: Churchill Livingstone; 1995: 479-98.
23 Mollison PL, Engelfriet CP, Contreas M, Lewis ABO. Ii and P groups. In: Blood transfusion in clinical medicine. 9th edition. Mollison PL, Engelfriet CP, Contreas M. Oxford: Blackwell Scientific Publications; 1993: 148-203.
24 Dobson A, Ikin EW. The ABO blood groups in the United Kingdom: frequencies based on a very large sample. J Pathol Bacteriol 1946; 58: 221-7.
25 Santoso S, Kiefel V, Mueller-Eckhardt C. Blood group A and B determinants are expressed on platelet glycoproteins IIa, IIIa and Ib. Thromb Haemost 1991; 65: 196-201.
26 Economidou J, Hughes-Jones NC, Gardner B. Quantitative measurements concerning A and B antigen sites. Vox Sang 1967; 12: 321-8.
27 Clausen HC, Levery SB, Nudelman E, Tsuchiya S, Hakomori S-I. Repetitive A epitope (type 3 chain A) defined by blood group A1-specific monoclonal antibody TH-1: chemical basis of qualitative A1 and A2 distinction. Proc Natl Acad Sci USA 1985; 82: 1199-203.
28 Sarode R, Goldstein J, Sussman II, Nagel RL, Tsai H. Role of A and B blood group antigens in the expression of adhesive activity of von Willebrand factor. Br J Haematol 2000; 109: 857-64.
29 Ernst C, Thurin J, Atkinson B, Wurzel H, Herlyn M, Stromberg N, Civin C, Koprowski H. Monoclonal antibody localization of A and B isoantigens in normal and malignant fixed human tissues. Am J Pathol 1984; 117: 451-61.
30 Aird WC, Edelbeerg JM, Weiler-Guettler H, Simmons WW, Smith TW, Rosenberg RD. Vascular bed-specific expression of an endothelial cell gene is programmed by the tissue microenvironment. J Cell Biol 1997; 138: 1117-24.
31 Yamamoto F, Clausen H, White T, Marken J, Hakomori S. Molecular genetic basis of the histo-blood group ABO system. Nature 1990; 345: 229-33.