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Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts

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Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts. / Beckmann, Lennart; Rolling, Christina Charlotte; Voigtländer, Minna; Mäder, Jonathan; Klingler, Felix; Schulenkorf, Anita; Lehr, Carina; Bokemeyer, Carsten; Ruf, Wolfram; Langer, Florian.

In: CANCERS, Vol. 13, No. 16, 04.08.2021, p. 3941.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Beckmann, L, Rolling, CC, Voigtländer, M, Mäder, J, Klingler, F, Schulenkorf, A, Lehr, C, Bokemeyer, C, Ruf, W & Langer, F 2021, 'Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts', CANCERS, vol. 13, no. 16, pp. 3941. https://doi.org/10.3390/cancers13163941

APA

Beckmann, L., Rolling, C. C., Voigtländer, M., Mäder, J., Klingler, F., Schulenkorf, A., Lehr, C., Bokemeyer, C., Ruf, W., & Langer, F. (2021). Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts. CANCERS, 13(16), 3941. https://doi.org/10.3390/cancers13163941

Vancouver

Beckmann L, Rolling CC, Voigtländer M, Mäder J, Klingler F, Schulenkorf A et al. Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts. CANCERS. 2021 Aug 4;13(16):3941. https://doi.org/10.3390/cancers13163941

Bibtex

@article{387f2bc5d4ba4feaa0ae2eac588ae920,
title = "Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts",
abstract = "Aberrant expression of tissue factor (TF) by transformed myeloblasts and inflammatory monocytes drives coagulation activation in acute myeloid leukemia (AML). Although regulation of TF procoagulant activity (PCA) involves thiol-disulfide exchange reactions, the specific role of protein disulfide isomerase (PDI) and other thiol isomerases in AML-associated TF biology is unclear. THP1 cells and peripheral blood mononuclear cells (PBMCs) from healthy controls or AML patients were analyzed for thiol isomerase-dependent TF production under various experimental conditions. Total cellular and membrane TF antigen, TF PCA and TF mRNA were analyzed by ELISA, flow cytometry, clotting or Xa generation assay and qPCR, respectively. PBMCs and THP1 cells showed significant insulin reductase activity, which was inhibited by bacitracin or rutin. Co-incubation with these thiol isomerase inhibitors prevented LPS-induced TF production by CD14-positive monocytes and constitutive TF expression by THP1 cells and AML blasts. Downregulation of the TF antigen was mainly restricted to the cryptic pool of TF, efficiently preventing phosphatidylserine-dependent TF activation by daunorubicin, and at least partially regulated on the mRNA level in LPS-stimulated monocytes. Our study thus delineates a complex role of thiol isomerases in the regulation of myeloid TF PCA, with PDI being a promising therapeutic target in the management of AML-associated coagulopathies.",
author = "Lennart Beckmann and Rolling, {Christina Charlotte} and Minna Voigtl{\"a}nder and Jonathan M{\"a}der and Felix Klingler and Anita Schulenkorf and Carina Lehr and Carsten Bokemeyer and Wolfram Ruf and Florian Langer",
year = "2021",
month = aug,
day = "4",
doi = "10.3390/cancers13163941",
language = "English",
volume = "13",
pages = "3941",
journal = "CANCERS",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "16",

}

RIS

TY - JOUR

T1 - Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts

AU - Beckmann, Lennart

AU - Rolling, Christina Charlotte

AU - Voigtländer, Minna

AU - Mäder, Jonathan

AU - Klingler, Felix

AU - Schulenkorf, Anita

AU - Lehr, Carina

AU - Bokemeyer, Carsten

AU - Ruf, Wolfram

AU - Langer, Florian

PY - 2021/8/4

Y1 - 2021/8/4

N2 - Aberrant expression of tissue factor (TF) by transformed myeloblasts and inflammatory monocytes drives coagulation activation in acute myeloid leukemia (AML). Although regulation of TF procoagulant activity (PCA) involves thiol-disulfide exchange reactions, the specific role of protein disulfide isomerase (PDI) and other thiol isomerases in AML-associated TF biology is unclear. THP1 cells and peripheral blood mononuclear cells (PBMCs) from healthy controls or AML patients were analyzed for thiol isomerase-dependent TF production under various experimental conditions. Total cellular and membrane TF antigen, TF PCA and TF mRNA were analyzed by ELISA, flow cytometry, clotting or Xa generation assay and qPCR, respectively. PBMCs and THP1 cells showed significant insulin reductase activity, which was inhibited by bacitracin or rutin. Co-incubation with these thiol isomerase inhibitors prevented LPS-induced TF production by CD14-positive monocytes and constitutive TF expression by THP1 cells and AML blasts. Downregulation of the TF antigen was mainly restricted to the cryptic pool of TF, efficiently preventing phosphatidylserine-dependent TF activation by daunorubicin, and at least partially regulated on the mRNA level in LPS-stimulated monocytes. Our study thus delineates a complex role of thiol isomerases in the regulation of myeloid TF PCA, with PDI being a promising therapeutic target in the management of AML-associated coagulopathies.

AB - Aberrant expression of tissue factor (TF) by transformed myeloblasts and inflammatory monocytes drives coagulation activation in acute myeloid leukemia (AML). Although regulation of TF procoagulant activity (PCA) involves thiol-disulfide exchange reactions, the specific role of protein disulfide isomerase (PDI) and other thiol isomerases in AML-associated TF biology is unclear. THP1 cells and peripheral blood mononuclear cells (PBMCs) from healthy controls or AML patients were analyzed for thiol isomerase-dependent TF production under various experimental conditions. Total cellular and membrane TF antigen, TF PCA and TF mRNA were analyzed by ELISA, flow cytometry, clotting or Xa generation assay and qPCR, respectively. PBMCs and THP1 cells showed significant insulin reductase activity, which was inhibited by bacitracin or rutin. Co-incubation with these thiol isomerase inhibitors prevented LPS-induced TF production by CD14-positive monocytes and constitutive TF expression by THP1 cells and AML blasts. Downregulation of the TF antigen was mainly restricted to the cryptic pool of TF, efficiently preventing phosphatidylserine-dependent TF activation by daunorubicin, and at least partially regulated on the mRNA level in LPS-stimulated monocytes. Our study thus delineates a complex role of thiol isomerases in the regulation of myeloid TF PCA, with PDI being a promising therapeutic target in the management of AML-associated coagulopathies.

U2 - 10.3390/cancers13163941

DO - 10.3390/cancers13163941

M3 - SCORING: Journal article

C2 - 34439096

VL - 13

SP - 3941

JO - CANCERS

JF - CANCERS

SN - 2072-6694

IS - 16

ER -