Platelet-leukocyte interactions in thrombosis

  • Chiara Cerletti
    Corresponding author at: Research Laboratories, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica, Largo Gemelli, 1, 86100 CAMPOBASSO, Italy. Tel.: +39 0874 312 277; fax: +39 0874 312 710.
    Research Laboratories, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica, 86100 Campobasso, Italy
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  • Chiara Tamburrelli
    Research Laboratories, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica, 86100 Campobasso, Italy
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  • Author Footnotes
    1 Present address: Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
    Benedetta Izzi
    1 Present address: Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
    Research Laboratories, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica, 86100 Campobasso, Italy
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  • Francesco Gianfagna
    Research Laboratories, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica, 86100 Campobasso, Italy
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  • Giovanni de Gaetano
    Research Laboratories, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica, 86100 Campobasso, Italy
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  • Author Footnotes
    1 Present address: Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
Published:November 11, 2011DOI:


      Activated platelets may adhere to leukocytes and form circulating mixed aggregates. The latter are considered a reliable marker of a prothrombotic state and are associated with several cardiovascular conditions. The molecular mechanisms responsible of this cellular interaction include a central role of platelet P-selectin and of P-selectin glycoprotein ligand-1 (PSGL-1), its counter receptor on leukocytes in a signaling cascade, resulting in the activation of the beta-2 integrin Mac-1 and in the firm adhesion between the two cell types. The interaction of P-selectin with PSGL-1 also induces upregulation of leukocyte tissue factor, biosynthesis of several cytokines and other inflammatory reactions, thereby contributing to the thrombotic progression.
      In this review the main determinants of mixed aggregate formation, the heritability component, the major pathological conditions associated with higher levels of mixed aggregates in the circulation will be discussed. Besides current anti-platelet or antithrombotic drugs, natural compounds, such as the polyphenols present in vegetable foods and red wine, have been tested for their inhibitory effect on mixed aggregate formation. The promising results shown by studies in vitro and in experimental animal models, remain to be carefully investigated in humans. Platelet–leukocyte aggregates provide a novel link between inflammation and thrombosis, two central processes in atherogenesis. A better understanding of the role of platelet–leukocyte interactions in athero-thrombosis will be instrumental for the progress of prevention and treatment of ischaemic cardiovascular disease.


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