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Inhibition of thrombin-induced platelet aggregation using human single-chain Fv antibodies specific for TREM-like transcript-I

  1. Author:
    Giomarelli, B.
    Washington, V. A.
    Chisholm, M. M.
    Quigley, L.
    McMahon, J. B.
    Mori, T.
    McVicar, D. W.

  2. Author Address

    NCI, Mol Targets Dev Program, Frederick, MD 21702 USA. NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. Univ Cent Caribe, Dept Anat & Cell Biol, Bayamon, PR USA.;McVicar, DW, NCI, Mol Targets Dev Program, 560 Rm 31-46, Frederick, MD 21702 USA.;McvicarD@mail.nih.gov
    1. Year: 2007
    2. Date: Jun
  2. Journal: Thrombosis and Haemostasis
    1. 97
    2. 6
    3. Pages: 955-964
  4. Type of Article: Article
  5. ISSN: 0340-6245
  1. 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 naive 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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External Sources

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  2. DOI: 10.1160/th06-08-0456
  3. View record in Web of Science®
  4. WOS: 000247309000013

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