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Blood, 1 February 2007, Vol. 109, No. 3, pp. 995-1002. Prepublished online as a Blood First Edition Paper on September 26, 2006; DOI 10.1182/blood-2006-02-004945.
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Eosinophils are a major intravascular location for tissue factor storage and exposure1 Vaskuläre Biologie und Hämostase, Institut für Klinische Chemie, Ludwig-Maximilians-Universität, Munich, Germany; 2 Anatomie and Zellbiologie, Universität des Saarlandes, Homburg, Germany; 3 Department of Physiology and Biophysics, Immunology Research Group, University of Calgary, AB, Canada; and 4 Institut für Pathologie, Technische Universität Dresden, Germany Blood cell progenitors were scanned for the presence of the coagulation starter protein tissue factor (TF) by immunoelectron microscopy. Thereby, substantial TF expression was observed in the precursor cells of eosinophils. TF levels were lower in basophil precursors and barely detectable in neutrophil progenitors. In peripheral blood immediately processed to avoid activation of the TF gene, mature eosinophils were found to considerably express TF, unique among the granulocyte and monocyte fractions. TF was preferentially located in the specific granules in resting eosinophils. Platelet-activating factor (PAF), and more pronounced, granulocyte-macrophage colony-stimulating factor (GM-CSF) plus PAF, caused translocation of preformed TF to the eosinophil cell membrane. GM-CSF/PAF also increased the TF transcript levels. The activated eosinophils exhibited procoagulant activity that was abrogated by TF inhibition. Targeting the extracellular domain of TF with specific antibodies markedly suppressed the initial phase of the eosinophil passage across the IL-4activated endothelium. Eosinophil rolling and firm adhesion remained unaffected. This suggests that TF specifically facilitates the early transendothelial migration of the eosinophils. In summary, eosinophils maintain a high TF expression during maturation, providing a main source of preformed TF in blood, which might be relevant for the thrombogenesis promoted by hypereosinophilic conditions.
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