Polymorphonuclear neutrophils (PMNs) play a key role in host defense. However, their massive accu... more Polymorphonuclear neutrophils (PMNs) play a key role in host defense. However, their massive accumulation at the site of inflammation can delay regenerative healing processes and can initiate pathological inflammatory processes. Thus, the efficient clearance of PMNs mediated by the induction of regulated cell death is a key process preventing the development of these pathological conditions. Myeloperoxidase (MPO), a highly abundant enzyme in PMN granules, primarily connected with PMN defense machinery, is suggested to play a role in PMN-regulated cell death. However, the contribution of MPO to the mechanisms of PMN cell death remains incompletely characterized. Herein, the process of the cell death of mouse PMNs induced by three different stimuli – phorbol 12-myristate 13-acetate (PMA), opsonized streptococcus (OST), and N-formyl-met-leu-phe (fMLP) – was investigated. MPO-deficient PMNs revealed a significantly decreased rate of cell death characterized by phosphatidylserine surface...
Additional file 1: Figure S1. ROC curve showing the ability of serum circulating nucleosomes to d... more Additional file 1: Figure S1. ROC curve showing the ability of serum circulating nucleosomes to discriminate patients with CVH score ≤ 5 (AUC = 0.811; 95% CI = 0.676–0.945; p = 0.002). Figure S2. Circulating nucleosome levels are stable between patients with and without abnormal cardiac remodeling. Circulating nucleosomes are assayed by ELISA in Kardiovize participants (n = 120) and expressed as absorbance. The data represent the median and interquartile range and are compared using the Mann-Whitney U test. Figure S3. Circulating trimethyl histone H3K4 (M3K4m3) levels are stable across body mass index categories. The data represent the median and interquartile range and are compared using the Mann-Whitney U test. Table S1. Echocardiographic parameters of Kardiovize participants according to BMI categories.
An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The line of v-myb-transformed chicken monoblasts BM2 constitutively express v-myb oncogene of AMV... more The line of v-myb-transformed chicken monoblasts BM2 constitutively express v-myb oncogene of AMV. v-Myb causes differentiation block, high proliferation rate and resistance to apoptosis similarly as in v-myb-transformed myeloid precursor primary cells. Differentiation capability of BM2 cells to macrophage-like cells can resume by phorbol esters that activate PKC and transcription from promoters containing TRE. The fact that transcription factor AP-1 binds TRE prompted us to investigate the role of individual components of AP-1 - the Jun and Fos proteins in regulation of differentiation, proliferation and apoptosis of BM2 cells. We ectopically expressed c-Jun, c-Fos, v-Jun and v-Fos proteins in BM2 cells and compared their effects. We found that c-Fos but not c-Jun protein was capable to induce apoptosis of BM2 cells. Interestingly, transforming variant of the Fos protein (v-Fos) lost capacity of its cellular precursor to cause apoptosis of BM2 cells. On contrary, c-Jun but not c-Fo...
Wound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation ... more Wound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation of this cytotoxicity to clinical settings is unclear. We applied dressings with various forms of silver on porcine skin ex vivo and investigated silver penetration and DNA damage. We assessed antimicrobial efficacy, cytotoxicity to skin cells, and immune response induced by the dressings. All dressings elevated the DNA damage marker γ-H2AX and the expression of stress-related genes in explanted skin relative to control. This corresponded with the amount of silver in the skin. The dressings reduced viability, induced oxidative stress and DNA damage in skin cells, and induced the production of pro-inflammatory IL-6 by monocytes. The oxidative burst and viability of activated neutrophils decreased. The amount of silver released into the culture medium varied among the dressings and correlated with in vitro toxicity. However, antimicrobial efficiencies did not correlate strongly with the amo...
The aim of the study was to test the effect of experimental conditions such as light radiation an... more The aim of the study was to test the effect of experimental conditions such as light radiation and temperature on chemiluminescence (CL) of 10−2–10−5 mol/L lucigenin dissolved in various types of solvents. Irradiation by UV light (280, 297, 313 or 400 nm) induced a significant increase in CL of lucigenin dissolved in borate buffer. This effect was the most obvious for 10−2–10−3 mol/L lucigenin. All wavelengths used had a similar effect. UV irradiation did not induce changes in the CL activity of lucigenin dissolved in dH2O or in dimethyl sulphoxide (DMSO). Different results for various solvents were not dependent on pH. The CL activity of 10−2 mol/L and 10−3 mol/L lucigenin dissolved in borate buffer increased depending on the solution temperature (25°C, 30°C, 37°C or 40°C) already at the beginning of the analysis, with a further increase during 16 h incubation period. It can be summarized that temperatures higher than 25°C and intensive light irradiation are among those factors whic...
Background— The nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and the leuk... more Background— The nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and the leukocyte-derived hemoprotein myeloperoxidase (MPO) are associated with cardiovascular diseases. Activation of monocytes and polymorphonuclear neutrophils (PMNs) with concomitant release of MPO is regulated in a nitric oxide–dependent fashion. The aim of the study was to investigate a potential 2-way interaction between ADMA and MPO. Methods and Results— Ex vivo, ADMA uptake by isolated human PMNs, the principal source of MPO in humans, significantly impaired nitric oxide synthase activity determined by gas chromatography–mass spectrometry. In humans, short-term ADMA infusion (0.0125 mg · kg −1 · min −1 ) significantly increased MPO plasma concentrations. Functionally, PMN exposure to ADMA enhanced leukocyte adhesion to endothelial cells, augmented NADPH oxidase activity, and stimulated PMN degranulation, resulting in release of MPO. In vivo, a 28-day ADMA infusion (250 μmol · kg −1 · d −1 )...
Polymorphonuclear neutrophils (PMNs) play a key role in host defense. However, their massive accu... more Polymorphonuclear neutrophils (PMNs) play a key role in host defense. However, their massive accumulation at the site of inflammation can delay regenerative healing processes and can initiate pathological inflammatory processes. Thus, the efficient clearance of PMNs mediated by the induction of regulated cell death is a key process preventing the development of these pathological conditions. Myeloperoxidase (MPO), a highly abundant enzyme in PMN granules, primarily connected with PMN defense machinery, is suggested to play a role in PMN-regulated cell death. However, the contribution of MPO to the mechanisms of PMN cell death remains incompletely characterized. Herein, the process of the cell death of mouse PMNs induced by three different stimuli – phorbol 12-myristate 13-acetate (PMA), opsonized streptococcus (OST), and N-formyl-met-leu-phe (fMLP) – was investigated. MPO-deficient PMNs revealed a significantly decreased rate of cell death characterized by phosphatidylserine surface...
Additional file 1: Figure S1. ROC curve showing the ability of serum circulating nucleosomes to d... more Additional file 1: Figure S1. ROC curve showing the ability of serum circulating nucleosomes to discriminate patients with CVH score ≤ 5 (AUC = 0.811; 95% CI = 0.676–0.945; p = 0.002). Figure S2. Circulating nucleosome levels are stable between patients with and without abnormal cardiac remodeling. Circulating nucleosomes are assayed by ELISA in Kardiovize participants (n = 120) and expressed as absorbance. The data represent the median and interquartile range and are compared using the Mann-Whitney U test. Figure S3. Circulating trimethyl histone H3K4 (M3K4m3) levels are stable across body mass index categories. The data represent the median and interquartile range and are compared using the Mann-Whitney U test. Table S1. Echocardiographic parameters of Kardiovize participants according to BMI categories.
An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The line of v-myb-transformed chicken monoblasts BM2 constitutively express v-myb oncogene of AMV... more The line of v-myb-transformed chicken monoblasts BM2 constitutively express v-myb oncogene of AMV. v-Myb causes differentiation block, high proliferation rate and resistance to apoptosis similarly as in v-myb-transformed myeloid precursor primary cells. Differentiation capability of BM2 cells to macrophage-like cells can resume by phorbol esters that activate PKC and transcription from promoters containing TRE. The fact that transcription factor AP-1 binds TRE prompted us to investigate the role of individual components of AP-1 - the Jun and Fos proteins in regulation of differentiation, proliferation and apoptosis of BM2 cells. We ectopically expressed c-Jun, c-Fos, v-Jun and v-Fos proteins in BM2 cells and compared their effects. We found that c-Fos but not c-Jun protein was capable to induce apoptosis of BM2 cells. Interestingly, transforming variant of the Fos protein (v-Fos) lost capacity of its cellular precursor to cause apoptosis of BM2 cells. On contrary, c-Jun but not c-Fo...
Wound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation ... more Wound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation of this cytotoxicity to clinical settings is unclear. We applied dressings with various forms of silver on porcine skin ex vivo and investigated silver penetration and DNA damage. We assessed antimicrobial efficacy, cytotoxicity to skin cells, and immune response induced by the dressings. All dressings elevated the DNA damage marker γ-H2AX and the expression of stress-related genes in explanted skin relative to control. This corresponded with the amount of silver in the skin. The dressings reduced viability, induced oxidative stress and DNA damage in skin cells, and induced the production of pro-inflammatory IL-6 by monocytes. The oxidative burst and viability of activated neutrophils decreased. The amount of silver released into the culture medium varied among the dressings and correlated with in vitro toxicity. However, antimicrobial efficiencies did not correlate strongly with the amo...
The aim of the study was to test the effect of experimental conditions such as light radiation an... more The aim of the study was to test the effect of experimental conditions such as light radiation and temperature on chemiluminescence (CL) of 10−2–10−5 mol/L lucigenin dissolved in various types of solvents. Irradiation by UV light (280, 297, 313 or 400 nm) induced a significant increase in CL of lucigenin dissolved in borate buffer. This effect was the most obvious for 10−2–10−3 mol/L lucigenin. All wavelengths used had a similar effect. UV irradiation did not induce changes in the CL activity of lucigenin dissolved in dH2O or in dimethyl sulphoxide (DMSO). Different results for various solvents were not dependent on pH. The CL activity of 10−2 mol/L and 10−3 mol/L lucigenin dissolved in borate buffer increased depending on the solution temperature (25°C, 30°C, 37°C or 40°C) already at the beginning of the analysis, with a further increase during 16 h incubation period. It can be summarized that temperatures higher than 25°C and intensive light irradiation are among those factors whic...
Background— The nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and the leuk... more Background— The nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and the leukocyte-derived hemoprotein myeloperoxidase (MPO) are associated with cardiovascular diseases. Activation of monocytes and polymorphonuclear neutrophils (PMNs) with concomitant release of MPO is regulated in a nitric oxide–dependent fashion. The aim of the study was to investigate a potential 2-way interaction between ADMA and MPO. Methods and Results— Ex vivo, ADMA uptake by isolated human PMNs, the principal source of MPO in humans, significantly impaired nitric oxide synthase activity determined by gas chromatography–mass spectrometry. In humans, short-term ADMA infusion (0.0125 mg · kg −1 · min −1 ) significantly increased MPO plasma concentrations. Functionally, PMN exposure to ADMA enhanced leukocyte adhesion to endothelial cells, augmented NADPH oxidase activity, and stimulated PMN degranulation, resulting in release of MPO. In vivo, a 28-day ADMA infusion (250 μmol · kg −1 · d −1 )...
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