Eosinophils are a major intravascular location for tissue factor storage and exposure

Vaskuläre Biologie und Hämostaste, Institut für Klinische Chemie, Ludwig-Maximilians-Universität, Munich, Germany.
Blood (Impact Factor: 10.45). 03/2007; 109(3):995-1002. DOI: 10.1182/blood-2006-02-004945
Source: PubMed


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-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 relevant for the thrombogenesis promoted by hypereosinophilic conditions.

  • Source
    • "Eosinophils contain several granule-associated molecules that play a role in the occurrence of thrombosis and vascular injury. Eosinophils can increase the risk of thrombosis through leukocyte and platelet stimulation and the release of tissue factor (20,21). These effects contribute to procoagulation by preventing the activation of thrombin and by inducing fibrin formation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: The pathophysiology of coronary slow flow has not been clearly defined, although multiple abnormalities including arteritis, endothelial dysfunction, and atherothrombosis, have been reported. It is known that eosinophils play an important role in inflammation, endothelial dysfunction, and thrombosis. We aimed to compare the eosinophil counts of coronary slow flow patients versus healthy controls. METHODS: This study included 50 coronary slow flow patients (19 males, mean age 65.6±13.7 years) and 30 healthy controls (10 males, mean age 57.86±11.6 years). These participants were evaluated using concurrent routine biochemical tests as well as neutrophil, lymphocyte, and eosinophil counts and mean platelet volume (MPV), which were obtained from the whole blood count. These parameters were compared between groups. RESULTS: The baseline characteristics of the study groups were comparable. The coronary slow flow patients had a higher mean platelet volume and eosinophil count than the control group (8.38±0.86 vs 6.28±1.6 fL and 0.31±0.42 vs 0.09±0.05; p<0.001 and 0.008, respectively). CONCLUSION: Our study demonstrated a relationship between eosinophil count and MPV in patients with coronary slow flow.
    Full-text · Article · May 2014 · Clinics (São Paulo, Brazil)
  • Source
    • "TF-exposing microparticles derived from eosinophils and neutrophils have been described in related eosinophilic diseases, like Churg Strauss vasculitis and bullous pemphigoid [38-40]. However, eosinophils as the potential source of coagulant TF-exposing microparticles remain controversial, since TF mRNA is below the detection limit in both resting and stimulated eosinophils [41,42]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance. 28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation). 13 patients with mild asthma (6 females, 19-29y) and 11 healthy controls (10 females, 19-31y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01).Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1. Experimental rhinovirus infection induces procoagulant changes in the airways of patients with asthma through increased activity of tissue factor-exposing microparticles. These microparticle-associated procoagulant changes are associated with both neutrophilic and eosinophilic inflammation. Systemic activation of haemostasis increases with Rhinoviral load.Trial registration: This trial was registered at the Dutch trial registry ( NTR1677.
    Full-text · Article · Feb 2014 · Respiratory research
  • Source
    • "This could be explained by the fact that the inflammatory state present in BP is not confined to the skin but also involves vascular endothelium [77], as does the pathogenesis of atherosclerosis, atheroma plaque rupture, and thrombosis [78]. Also, the inflammatory response in BP involves raised levels of eosinophils not only in the skin lesions but also in peripheral blood [79] and it has been shown that eosinophil granulocytes are an important source of tissue factor, the initiator of blood coagulation, in human blood [80, 81]. In addition, there is some evidence that antiphospholipid antibodies are present in the serum of BP patients [82]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Collagen XVII is a nonfibril-forming transmembrane collagen, which functions as both a matrix protein and a cell-surface receptor. It is particularly copious in the skin, where it is known to be a structural component of hemidesmosomes. In addition, collagen XVII has been found to be present in the central nervous system, thus offering an explanation for the statistical association between bullous pemphigoid, in which autoimmunity is directed against dermal collagen XVII, and neurological diseases. In support of the hypothesis that collagen XVII serves as a shared antigen mediating an immune response between skin and brain, research on animal and human tissue, as well as numerous epidemiological and case studies, is presented.
    Full-text · Article · Jun 2013 · Clinical and Developmental Immunology
Show more