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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.
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Submitted February 21, 2006
Accepted September 15, 2006
Eosinophils are a major intravascular location for
tissue factor storage and exposure
Christine Moosbauer, Eberhard Morgenstern, Susan L. Cuvelier, Davit Manukyan, Kiril Bidzhekov, Sybille Albrecht, Peter Lohse, Kamala D. Patel, and Bernd Engelmann*
Clinical Chemistry, Ludwig-Maximilians-University, Munich, Germany
Anatomy and Cell Biology, University of Saarland, Hamburg, Germany
Department of Physiology and Biophysics, University of Calgary, Alberta, Canada
Pathology, University of Dresden, Dresden, Germany
* Corresponding author; email: bernd.engelmann{at}med.uni-muenchen.de.
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 (GMCSF) plus PAF, caused translocation of preformed TF to the eosinophil cell membrane. GMCSF/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-4 activated 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 of relevance for the thrombogenesis promoted by hypereosinophilic conditions.
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