Regulation of Monocyte Tissue Factor Activity by Allogeneic and Xenogeneic Endothelial Cells

Kopp, Christoph W.; Siegel, Jonathan H.; Anrather, Josef; Winkler, Hans; Grey, Shane T.; Kaczmarek, Elżbieta; Bach, Fritz H.; Geczy, Carolyn L.; Robson, Simon C.

doi:10.1055/s-0037-1614939

Cited by 35 publications

(30 citation statements)

References 36 publications

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“…In vitro model to induce the expression of human and pig TF Adherent pig AECs and monocytes were pre-incubated with 5% human plasma for 8 hours to induce the expression of pig or human TF, respectively, on the cell surface [5,18,19]. Human plasma was drawn from volunteers with type A blood.…”

Section: Cell Culturementioning

confidence: 99%

Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model

Yue

et al. 2015

Cell Physiol Biochem

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Background: The activation of tissue factor (TF) is one of the major reasons for coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor pathway inhibitor (TFPI) is the most important inhibitor of TF. Studies have demonstrated species incompatibility between pig TFPI and human TF. Methods: A pig-to-macaque heterotopic auxiliary liver transplantation model was established to determine the origin of activated TF. Chimeric proteins of human and pig TFPI were constructed to assess the role of Kunitz domains in species incompatibility. Immortalised pig bone marrow mesenchymal stem cells transfected with human TFPI were tested for their ability to inhibit clotting in vitro. Results: TF from recipient was activated early after liver xenotransplantation. Pig TFPI Kunitz domain 2 bound human FXa, but Kunitz domain 1 did not effectively inhibit human TF/FVIIa. Immortalised pig bone marrow mesenchymal cells (BMSCs) transfected with human TFPI showed a prolonged recalcification time in vitro and in a rodent model. Conclusion: Recipient TF is relevant to dysregulated coagulation after xenotransplantation. Kunitz domain 1 plays the most important role in species incompatibility between pig TFPI and human TF, and clotting can be inhibited by human TFPI-transfected pig BMSCs. Our study shows a possible way to resolve the incompatibility of pig TFPI.

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Section: Cell Culturementioning

confidence: 99%

Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model

Yue

et al. 2015

Cell Physiol Biochem

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“…Tissue factory (TF) activity was measured with a two-stage chromogenic reaction as described previously (Kopp et al, 1998).…”

Section: Measurement Of Tissue Factor Activitymentioning

confidence: 99%

Carbon Monoxide Orchestrates a Protective Response through PPARγ

et al. 2006

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Carbon monoxide (CO) suppresses proinflammatory responses in macrophages reacting to LPS. We hypothesize that CO acts by inducing a molecule(s) that suppresses the inflammatory response to subsequent stress. Exposure of macrophages to CO alone in vitro produced a brief burst of mitochondrial-derived ROS, which led to expression of PPARgamma. PPARgamma expression proved essential for mediating the anti-inflammatory effects of CO. Blocking the CO-mediated increase in ROS generation prevented PPARgamma induction, and blocking PPARgamma prevented CO's anti-inflammatory effects. In a model of acute lung injury in mice, CO blocked expression of Egr-1, a central mediator of inflammation, and decreased tissue damage; inhibition of PPARgamma abrogated both effects. These data identify the mitochondrial oxidases as an (perhaps the) initial cellular target of CO and demonstrate that CO upregulates expression of PPARgamma via the mitochondria, which assures that a subsequent stress stimulus will lead to a cytoprotective as opposed to a proinflammatory phenotype.

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“…In a separate series of experiments, we found that the HKC-5 also express TFPI. It is common in such protease activated systems that the trigger and the inhibitor are produced by the same source, [29][30][31] probably to regulate cellular procoagulant activity in their milieu. In kidneys TFPI has been found in a normal and in a glomerulonephritis crescentic rabbit model, 32 33 where fibrin deposition could be a key mediator of injury, 32 through TF-mediated coagulation pathways.…”

Section: Discussionmentioning

confidence: 99%

Tissue factor expression by a human kidney proximal tubular cell line in vitro: a model relevant to urinary tissue factor secretion in disease?

Lwaleed

Vayro

Racusen³

et al. 2006

J Clin Pathol

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Aim: To study baseline and stimulated tissue factor (TF) production from a normal, albeit immortalised, human kidney proximal tubular cell line (HKC-5), in order to establish a model for investigating the role of inflammatory mediators in the increased urinary TF (uTF) seen in inflammatory and neoplastic disease. Methods: TF procoagulant activity, expression and secretion in HKC-5 cells were investigated using TF activity and antigen assays, fluorescence confocal microscopy and immunocytochemistry. TF expression in the HKC-5 cells was also studied using reverse transcription (RT)-PCR and its synthesis was suppressed using antisense oligodeoxynucleotide (ODN), directed against human TF mRNA. Cells were stimulated, after serum deprivation, with bacterial lipopolysaccharide (LPS), an agonist known to enhance TF expression in monocytes. They were also subject to serum starvation. Results: Analysis by RT-PCR showed TF production by stimulated and actively metabolising HKC-5 cells. Antisense ODN treatment resulted in approximately 50% suppression of TF synthesis compared to a mismatch ODN. The amount of TF produced by the HKC-5 cells was time dependent and coincides with a decrease in the intracellular TF levels. LPS up-regulated TF production in HKC-5 cells. Reducing fetal calf serum concentrations in the culture medium decreased TF production and secretion. Conclusion: Stimulated TF synthesis and secretion in vitro by HKC-5 cells is consistent with the hypothesis that uTF is produced by tubular cells influenced by mediators of disease states and provides a model for further mechanistic investigations.

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Regulation of Monocyte Tissue Factor Activity by Allogeneic and Xenogeneic Endothelial Cells

Cited by 35 publications

References 36 publications

Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model

Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model

Carbon Monoxide Orchestrates a Protective Response through PPARγ

Tissue factor expression by a human kidney proximal tubular cell line in vitro: a model relevant to urinary tissue factor secretion in disease?

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