Inhibition of thrombin-induced platelet aggregation using human single-chain Fv antibodies specific for TREM-like transcript-1.
Thromb Haemost
; 97(6): 955-63, 2007 Jun.
Article
in En
| MEDLINE
| ID: mdl-17549298
ABSTRACT
TREM-like transcript-1 (TLT-1) is a novel platelet membrane receptor, which has been recently characterized in mice. TLT-1 is expressed exclusively in platelets and megakaryocytes, and its expression is dramatically upregulated upon platelet activation, suggesting that it plays a unique role in hemostasis and/or thrombosis. In this study we identified and characterized highly specific human monoclonal antibodies that bind to TLT-1 by screening a naïve library of single chain Fv fragments (scFvs) displayed on filamentous phage (Thomlinson I library). These scFvs detected plate-bound TLT-1, captured soluble TLT-1, and readily reacted with cell-bound TLT-1 on transfectants and primary human platelets. Most importantly, anti-TLT-1 scFvs inhibited thrombin-mediated human platelet aggregation. This inhibition was specific for thrombin-induced aggregation and was reversible with higher doses of agonist. These data are the first to demonstrate a biological role for TLT-1 and its potential as a therapeutic target. The human scFvs isolated in this study may represent novel anti-platelet therapeutic agents.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood Platelets
/
Immunoglobulin Variable Region
/
Receptors, Immunologic
/
Thrombin
/
Platelet Aggregation
/
Fibrinolytic Agents
/
Antibodies, Monoclonal
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Thromb Haemost
Year:
2007
Document type:
Article
Affiliation country:
United States