Differential expression of tissue factor mRNA and protein expression in murine sepsis

Abstract

Tissue factor (TF) is a transmembrane protein, which is essential for initiation of the coagulation cascade. TF has been reported to play an important role in the progression of endotoxin (lipopolysaccharide, LPS)-mediated endotoxemia, being induced in numerous tissues, such as kidney, spleen and lung. We developed and validated a rabbit anti-murine TF peptide antiserum to localize TF protein in a murine sepsis model. TF protein distribution was compared to localization of TF mRNA and fibrin deposits, the ultimate resultant of procoagulant TF activity. Evident LPS mediated TF mRNA induction was observed in the tubular area at the cortico-medullar junction in the kidney, and TF activity was increased after 6 hours of endotoxemia. In the spleen, however, TF mRNA was induced in the interfollicular region upon LPS injection, corresponding to increased TF protein in the same area. The clusters of TF-protein positive cells in the spleen are predominantly granulocytes, but no TF mRNA expression was observed within these cells. Based on these observations and the presence of TF-protein positive granulocytes after splenectomy, we hypothesize that granulocytes take-up TF for transport to other locations in order to initiate fibrin formation or to induce pro-inflammatory gene expression upon interaction with factor VIIa.

Vascular Gas6 contributes to thrombogenesis and promotes tissue factor up-regulation after vessel injury in mice

“…24,42 The source of TF in venous thrombosis, whether produced from the endothelium, vascular smooth muscle, circulating cells, or microparticles, is still under debate. [43][44][45] Here we show that TF is up-regulated in the vascular wall in FeCl 3 -induced venous thrombosis. We isolated endothelial cells from mouse lung tissue and used thrombin as a procoagulant stimulus.…”

Plasma and IgGs from patients with lupus anticoagulant induce tissue factor in monocytes: a possible risk factor for thrombosis

“…This, however, is a controversial subject, as there are some reports of TF expression by granulocytes [10]. We believe that this is attributable to transfer of TF from monocytes as previously reported [6], and has also been indirectly proven in an in vivo endotoxemic model, where no TF mRNA was found in granulocytes of tissue containing TF antigen [11].…”

Tissue Factor and Cardiovascular Disease: Quo Vadis?

“…In addition to the de novo synthesis of TF in neutrophils, granulocytes may take up TF via TF-positive microparticles (MPs). 49 In contrast, in eosinophilic granulocytes and their progenitors cells, basal TF expression has been described. 50 Stimulation with granulocyte-macrophage colony-stimulating factor or platelet-activating factor, results in de novo TF transcription and translocation from the granules to the cell membrane 50 ; thus contributing to the pro-thrombotic state in hypereosinophilic syndromes.…”