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Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets

Nature volume 359, pages 848–851 (1992)Cite this article

Abstract

THE glycoprotein P-selectin is a cell adhesion molecule of stimulated platelets and endothelial cells, which mediates the interaction of these cells with neutrophils and monocytes1,2. It is a membrane component of cell storage granules3–6, and is a member of the selectin family which includes E-selectin and L-selectin7,8. P-selectin recognizes both lineage-specific carbohydrate ligands on monocytes and neutrophils, including the Lewis x antigen, sialic acid, and a protein component9–12. In inflammation and thrombosis, P-selectin may mediate the interaction of leukocytes with platelets bound in the region of tissue injury and with stimulated endothelium1,2. To evaluate the role of P-selectin in platelet–leukocyte adhesion in vivo, the accumulation of leukocytes within an experimental thrombus was explored in an arteriovenous shunt model in baboons13. A Dacron graft implanted within an arteriovenous shunt is thrombogenic, accumulating platelets and fibrin within its lumen. These bound platelets express P-selectin14. Here we show that antibody inhibition of leukocyte binding to P-selectin expressed on platelets immobilized on the graft blocks leukocyte accumulation and inhibits the deposition of fibrin within the thrombus. These results indicate that P-selectin is an important adhesion molecule on platelets, mediating platelet–leukocyte binding in vivo, that the presence of leukocytes in thrombi is mediated by P-selectin, and that these leukocytes promote fibrin deposition.

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Authors and Affiliations

  1. Center for Hemostasis and Thrombosis Research, Division of Hematology–Oncology, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA

    Theresa Palabrica, Barbara C. Furie, Susan A. Sajer & Bruce Furie

  2. Division of Cardiology, New England Medical Center and the Department of Medicine and Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA

    Theresa Palabrica & Mark Aronovitz

  3. Biogen Inc. 14 Cambridge Center, Cambridge, Massachusetts, 02142, USA

    Roy Lobb, Christopher Benjamin & Yen-Ming Hsu

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  1. Theresa Palabrica
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  7. Susan A. Sajer
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Palabrica, T., Lobb, R., Furie, B. et al. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature 359, 848–851 (1992). https://doi.org/10.1038/359848a0

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