Human Single Chain Antibodies Against Heparin: Selection, Characterization and Effect on Coagulation
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Authors
Van de Westerlo, Els M.A.
Smetsers, Toon F.C.M.
Dennissen, Michel A.B.A.
Linhardt, Robert J.
Veerkamp, Jacques H.
Van Muijen, Goos N.P.
Van Kuppevelt, Toin H.
Issue Date
2002-04-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Heparin, located in mast cells and basophilic granulocytes, is widely used as an anticoagulant. It belongs to a class of linear polysaccharides called glycosaminoglycans (GAGs). Using phage display technology, we have selected 19 unique human antiheparin antibodies. Some antibodies react almost exclusively with heparin, others also react with the structurally related heparan sulfate, and some with chondroitin sulfate. In all cases, sulfate groups are essential for binding. For activity of some antibodies, O-sulfation is more important than N-sulfation. Antibodies are reactive with heparin in mast cells. Each antibody showed a defined staining pattern on cryosections of rat kidney, pancreas, and testis. Enzymatic digestion with glycosidases on tissue sections further indicated that the antibodies are specific for GAGs. All antibodies recognize a unique epitope. The effect of the antibodies on heparin as an anticoagulant was also studied. There were 3 antibodies that were very effective inhibitors of heparin action in the activated partial thromboplastin time (APTT) clotting assay, and their effect was related to the amount of heparin bound. Some antibodies reacted strongly with the pentasaccharide, which interacts with antithrombin III. The human antibodies selected represent unique tools to study the structure, location, and function of heparin and related GAGs, and some may be used as blocking agents.
Description
Blood, 99, 2427-2433
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Human Single Chain Antibodies Against Heparin: Selection, Characterization and Effect on Coagulation, E.M.A. van de Westerlo, T.F.C.M. Smetsers, M.A.B.A. Dennissen, R.J. Linhardt, J.H. Veerkamp, G.N.P. van Muijen, T.H. van Kuppevelt, Blood, 99, 2427-2433, 2002.
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Volume
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PubMed ID
DOI
ISSN
64971