scholarly journals Inter-α inhibitor proteins maintain neutrophils in a resting state by regulating shape and reducing ROS production

2018 ◽  
Vol 2 (15) ◽  
pp. 1923-1934 ◽  
Author(s):  
Soe Soe Htwe ◽  
Hidenori Wake ◽  
Keyue Liu ◽  
Kiyoshi Teshigawara ◽  
Barbara S. Stonestreet ◽  
...  
Keyword(s):  
Resting State ◽  
Smooth Surface ◽  
Spherical Shape ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Ros Production ◽  
Concentration Dependent Manner ◽  
Key Points

Key Points IAIP, but not bikunin, maintains spherical shape, small size, and smooth surface of human neutrophils and supports capillary passage. IAIP reduced ROS production from neutrophils in a concentration-dependent manner probably through the p47phox phosphorylation on Ser328.

scholarly journals Titanium Dioxide Nanoparticles Induce Inhibitory Effects against Planktonic Cells and Biofilms of Human Oral Cavity Isolates of Rothia mucilaginosa, Georgenia sp. and Staphylococcus saprophyticus

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1564
Author(s):  
Saher Fatima ◽  
Khursheed Ali ◽  
Bilal Ahmed ◽  
Abdulaziz A. Al Kheraif ◽  
Asad Syed ◽  
...  
Keyword(s):  
Titanium Dioxide Nanoparticles ◽  
Anatase Phase ◽  
Spherical Shape ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Bacterial Cells ◽  
Gram Positive ◽  
Concentration Dependent Manner ◽  
Staphylococcus Saprophyticus ◽  
Rothia Mucilaginosa

Multi-drug resistant (MDR) bacterial cells embedded in biofilm matrices can lead to the development of chronic cariogenesis. Here, we isolated and identified three Gram-positive MDR oral cocci, (1) SJM-04, (2) SJM-38, and (3) SJM-65, and characterized them morphologically, biochemically, and by 16S rRNA gene-based phylogenetic analysis as Georgenia sp., Staphylococcus saprophyticus, and Rothia mucilaginosa, respectively. These three oral isolates exhibited antibiotic-resistance against nalidixic acid, tetracycline, cefuroxime, methicillin, and ceftazidime. Furthermore, these Gram positive MDR oral cocci showed significant (p < 0.05) variations in their biofilm forming ability under different physicochemical conditions, that is, at temperatures of 28, 30, and 42 °C, pH of 6.4, 7.4, and 8.4, and NaCl concentrations from 200 to 1000 µg/mL. Exposure of oral isolates to TiO2NPs (14.7 nm) significantly (p < 0.05) reduced planktonic cell viability and biofilm formation in a concentration-dependent manner, which was confirmed by observing biofilm architecture by scanning electron microscopy (SEM) and optical microscopy. Overall, these results have important implications for the use of tetragonal anatase phase TiO2NPs (size range 5–25 nm, crystalline size 13.7 nm, and spherical shape) as an oral antibiofilm agent against Gram positive cocci infections. We suggest that TiO2NPs pave the way for further applications in oral mouthwash formulations and antibiofilm dental coatings.

scholarly journals Modulatory Effect of Chelidonium majus Extract and Its Alkaloids on LPS-Stimulated Cytokine Secretion in Human Neutrophils

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 842 ◽  
Author(s):  
Sylwia Zielińska ◽  
Monika Ewa Czerwińska ◽  
Magdalena Dziągwa-Becker ◽  
Andrzej Dryś ◽  
Mariusz Kucharski ◽  
...  
Keyword(s):  
Biological Activities ◽  
Cytokine Secretion ◽  
Human Neutrophils ◽  
Root Extract ◽  
Dependent Manner ◽  
Chelidonium Majus ◽  
Concentration Dependent Manner ◽  
Cytotoxic Effects ◽  
Tnf Α ◽  
High Cytotoxicity

Due to certain differences in terms of molecular structure, isoquinoline alkaloids from Chelidonium majus engage in various biological activities. Apart from their well-documented antimicrobial potential, some phenanthridine and protoberberine derivatives as well as C. majus extract present with anti-inflammatory and cytotoxic effects. In this study, the LC–MS/MS method was used to determine alkaloids, phenolic acids, carboxylic acids, and hydroxybenzoic acids. We investigated five individually tested alkaloids (coptisine, berberine, chelidonine, chelerythrine, and sanguinarine) as well as C. majus root extract for their effect on the secretion of IL-1β, IL-8, and TNF-α in human polymorphonuclear leukocytes (neutrophils). Berberine, chelidonine, and chelerythrine significantly decreased the secretion of TNF-α in a concentration-dependent manner. Sanguinarine was found to be the most potent inhibitor of IL-1β secretion. However, the overproduction of IL-8 and TNF-α and a high cytotoxicity for these compounds were observed. Coptisine was highly cytotoxic and slightly decreased the secretion of the studied cytokines. The extract (1.25–12.5 μg/mL) increased cytokine secretion in a concentration-dependent manner, but an increase in cytotoxicity was also noted. The alkaloids were active at very low concentrations (0.625–2.5 μM), but their potential cytotoxic effects, except for chelidonine and chelerythrine, should not be ignored.

scholarly journals Identification of Constituents of Human Neutrophil Azurophil Granules That Mediate Fungistasis againstHistoplasma capsulatum

2000 ◽  
Vol 68 (10) ◽  
pp. 5668-5672 ◽  
Author(s):  
Simon L. Newman ◽  
Lisa Gootee ◽  
Joelle E. Gabay ◽  
Michael E. Selsted
Keyword(s):  
Human Neutrophil ◽  
Histoplasma Capsulatum ◽  
Cathepsin G ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Subsequent Growth ◽  
Concentration Dependent Manner ◽  
Fungistatic Activity ◽  
Maximum Inhibition ◽  
Azurophil Granule

ABSTRACT Previously we demonstrated that human neutrophils mediate potent and long-lasting fungistasis against Histoplasma capsulatumyeasts and that all of the fungistatic activity resides in the azurophil granules. In the present study, specific azurophil granule constituents with fungistatic activity were identified by incubation with H. capsulatum yeasts for 24 h and by quantifying the subsequent growth of yeasts via the incorporation of [3H]leucine. Human neutrophil defensins HNP-1, HNP-2, and HNP-3 inhibited the growth of H. capsulatum yeasts in a concentration-dependent manner with maximum inhibition at 8 μg/ml. At a concentration of 4 μg/ml, all possible paired combinations of defensins exhibited additive fungistatic activity against H. capsulatum yeasts. Cathepsin G and bactericidal-permeability-increasing protein (BPI) also mediated fungistasis against H. capsulatum in a concentration-dependent manner. The fungistatic activities of combinations of cathepsin G and BPI were additive, as were those of combinations of cathepsin G or BPI with HNP-1, HNP-2, and HNP-3. Lysozyme and elastase exhibited modest antifungal activity, and azurocidin and proteinase 3 exhibited no significant fungistasis against H. capsulatum yeasts. Thus, defensins, cathepsin G, and BPI are the major anti-H. capsulatum effector molecules in the azurophil granules of human neutrophils.

scholarly journals Serum of coronary atherosclerotic heart disease patients induces oxidative stress injury on endothelial cells

Pteridines ◽  
2018 ◽  
Vol 29 (1) ◽  
pp. 97-103
Author(s):  
Huichao Pan ◽  
Min Zhang
Keyword(s):  
Endothelial Cells ◽  
Heart Disease ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Treated Group ◽  
Dependent Manner ◽  
Ros Production ◽  
Concentration Dependent Manner ◽  
Stress Injury ◽  
Huvec Proliferation

AbstractEndothelial cell (EC) dysfunction has a fundamental role in the development of atherosclerosis, which leads to myocardial infarction and stroke. The aim of this study is to investigate the effect of serum from patients with coronary atherosclerotic heart disease (CAD) on endothelial cells and investigate the possible mechanism underlying these effects. Serum from 35 patients with CAD and 35 healthy volunteers was collected. Human umbilical vein endothelial cell (HUVEC) proliferation and apoptosis were assessed by a CCK‑8 assay and a flow cytometry assay, respectively. The synthesis of nitric oxide (NO) and reactive oxygen species (ROS) was measured using the nitrate reduction method and DCFH2-DA staining, respectively. The proliferation of HUVECs was inhibited by treatment with serum from CAD patients (P<0.05). Suppression of HUVEC proliferation by CAD serum occurred in a concentration-dependent manner. The synthesis of NO was also reduced in the CAD serum-treated group. Furthermore, the serum from CAD patients increased both apoptosis and intracellular ROS production in HUVECs. Moreover, treatment with tempol antagonized CAD serum-meditated HUVEC injuries. Taken together, these results suggest that HUVEC injury via CAD serum treatment is mediated by ROS production. Tempol may partly reverse this effect by abolishing HUVEC apoptosis.

scholarly journals Structural Characterization and Antioxidative Activity of Low-Molecular-Weights Beta-1,3-Glucan from the Residue of ExtractedGanoderma lucidumFruiting Bodies

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Pai-Feng Kao ◽  
Shwu-Huey Wang ◽  
Wei-Ting Hung ◽  
Yu-Han Liao ◽  
Chun-Mao Lin ◽  
...  
Keyword(s):  
Cell Death ◽  
High Performance ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Water Soluble ◽  
Dependent Manner ◽  
Ros Production ◽  
Fruiting Bodies ◽  
Concentration Dependent Manner

The major cell wall constituent ofGanoderma lucidum(G. lucidum) isβ-1,3-glucan. This study examined the polysaccharide from the residues of alkaline-extracted fruiting bodies using high-performance anion-exchange chromatography (HPAEC), and it employed nuclear magnetic resonance (NMR) and mass spectrometry (MS) to confirm the structures. We have successfully isolated low-molecular-weightβ-1,3-glucan (LMG), in high yields, from the waste residue of extracted fruiting bodies ofG. lucidum. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay evaluated the capability of LMG to suppress H2O2-induced cell death in RAW264.7 cells, identifying that LMG protected cells from H2O2-induced damage. LMG treatment decreased H2O2-induced intracellular reactive oxygen species (ROS) production. LMG also influenced sphingomyelinase (SMase) activity, stimulated by cell death to induce ceramide formation, and then increase cell ROS production. Estimation of the activities of neutral and acid SMasesin vitroshowed that LMG suppressed the activities of both neutral and acid SMases in a concentration-dependent manner. These results suggest that LMG, a water-solubleβ-1,3-glucan recycled from extracted residue ofG. lucidum, possesses antioxidant capability against H2O2-induced cell death by attenuating intracellular ROS and inhibiting SMase activity.

scholarly journals Decitabine Downregulates TIGAR to Induce Apoptosis and Autophagy in Myeloid Leukemia Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Lanzhu Li ◽  
Wenjie Liu ◽  
Qian Sun ◽  
Han Zhu ◽  
Ming Hong ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Dna Methyltransferase ◽  
Negative Impact ◽  
Cell Metabolism ◽  
Leukemia Cell ◽  
K562 Cells ◽  
Glycolytic Pathway ◽  
Dependent Manner ◽  
Ros Production ◽  
Concentration Dependent Manner

Decitabine (DAC) is a well-known DNA methyltransferase inhibitor, which has been widely used for the treatment of acute myeloid leukemia (AML). However, in addition to hypomethylation, DAC in AML is also involved in cell metabolism, apoptosis, and immunity. The TP53-induced glycolysis and apoptosis regulator (TIGAR) functions to inhabit glycolysis and protect cancer cells from reactive oxygen species- (ROS-) associated apoptosis. Our previous study revealed that TIGAR is highly expressed in myeloid leukemia cell lines and AML primary cells and associated with poor prognosis in adult patients with cytogenetically normal AML. In the present study, it was found that in a time- and concentration-dependent manner, DAC downregulates the TIGAR expression, induces ROS production, and promotes apoptosis in HL-60 and K562 cells. However, blocking the glycolytic pathway partially reversed the combined effects of DAC and TIGAR knockdown on apoptosis, ROS production, and cell cycle arrest, indicating that DAC induced apoptosis through the glycolytic pathway. Furthermore, TIGAR also has a negative impact on autophagy, while DAC treatment upregulates autophagy-related proteins LC3, Beclin-1, ATG3, and ATG-5, downregulates p62, and promotes the formation of autophagosomes, indicating that DAC may activate autophagy by downregulating TIGAR. Taken together, DAC plays an unmethylated role in inducing apoptosis and activating autophagy in myeloid leukemia by downregulating TIGAR.

scholarly journals Responsiveness of human neutrophils to interleukin-4: induction of cytoskeletal rearrangements, de novo protein synthesis and delay of apoptosis

1997 ◽  
Vol 325 (1) ◽  
pp. 147-153 ◽  
Author(s):  
Denis GIRARD ◽  
Robert PAQUIN ◽  
André D. BEAULIEUL
Keyword(s):  
Protein Synthesis ◽  
De Novo ◽  
Biological Activities ◽  
Interleukin 4 ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cytoskeletal Rearrangements ◽  
First Time ◽  
De Novo Protein Synthesis

Interleukin-4 (IL-4) and IL-13 are cytokines that share many biological activities. We have previously demonstrated that IL-13 affects a number of neutrophil responses, and here we extend our observations to IL-4. We present, for the first time, direct evidence for the presence of functional IL-4 receptors on human neutrophils. We report that IL-4 induces RNA synthesis in a concentration-dependent manner and, based on observations of the induction of morphological cell shape changes and spreading onto glass, we demonstrate that IL-4 activates neutrophil cytoskeletal rearrangements. We further show that IL-4 is a potent activator of de novo protein synthesis in neutrophils, and we identify by microsequencing one of these proteins as the cytoskeletal protein actin. We were also able to demonstrate for the first time that actin is cleaved into at least two fragments of ∼ 30 kDa (pI 5.4) and ∼ 25 kDa (pI 5.0) in neutrophils. Finally, we report that IL-4 delays neutrophil apoptosis, as assessed by morphological observations from cytocentrifuge preparations, as well as by measurement of differences in staining by flow cytometry with both propidium iodide and Hoechst reagent. Taken together, we conclude that IL-4 is a more potent neutrophil agonist than previously believed. We discuss the possibility that the induction of the de novo synthesis of actin by IL-4 is related to the mechanism by which this cytokine delays apoptosis; in addition, the cleavage of this protein is likely to contribute to the apoptotic process.

scholarly journals Neutrophil Extracellular Traps Activate Proinflammatory Functions of Human Neutrophils

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Dömer ◽  
Tabea Walther ◽  
Sonja Möller ◽  
Martina Behnen ◽  
Tamás Laskay
Keyword(s):  
B Cell ◽  
Adaptive Immune System ◽  
Neutrophil Extracellular Traps ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Extracellular Traps ◽  
Proinflammatory Role

Neutrophil extracellular traps (NETs) consist of decondensed nuclear chromatin that is associated with proteins and are released by neutrophils during an inflammatory response. Released NETs are able to capture pathogens, prevent their dissemination and potentially kill them via antimicrobial peptides and proteins that are associated with the decondensed chromatin. In addition to their antimicrobial functions, NETs have also been shown to exert immunomodulatory effects by activation and differentiation of macrophages, dendritic cells and T cells. However, the effect of NETs on neutrophil functions is poorly understood. Here we report the first comprehensive study regarding the effects of NETs on human primary neutrophils in vitro. NETs were isolated from cultures of PMA-exposed neutrophils. Exposure of neutrophils to isolated NETs resulted in the activation of several neutrophil functions in a concentration-dependent manner. NETs induced exocytosis of granules, the production of reactive oxygen species (ROS) by the NADPH oxidase NOX2, NOX2-dependent NET formation, increased the phagocytosis and killing of microbial pathogens. Furthermore, NETs induced the secretion of the proinflammatory chemokine IL-8 and the B-cell-activating cytokine BAFF. We could show that the NET-induced activation of neutrophils occurs by pathways that involve the phosphorylation of Akt, ERK1/2 and p38. Taken together our results provide further insights into the proinflammatory role of NETs by activating neutrophil effector function and further supports the view that NETs can amplify inflammatory events. On the one hand the amplified functions enhance the antimicrobial defense. On the other hand, NET-amplified neutrophil functions can be involved in the pathophysiology of NET-associated diseases. In addition, NETs can connect the innate and adaptive immune system by inducing the secretion of the B-cell-activating cytokine BAFF.

scholarly journals Synthesis and Characterization of Sulfur and Sulfur-Selenium Nanoparticles Loaded on Reduced Graphene Oxide and Their Antibacterial Activity against Gram-Positive Pathogens

Nanomaterials ◽  
2022 ◽  
Vol 12 (2) ◽  
pp. 191
Author(s):  
Rashmi Niranjan ◽  
Saad Zafar ◽  
Bimlesh Lochab ◽  
Richa Priyadarshini
Keyword(s):  
Antibacterial Activity ◽  
Graphene Oxide ◽  
Reduced Graphene Oxide ◽  
Antimicrobial Agents ◽  
Antibacterial Properties ◽  
Spherical Shape ◽  
Dependent Manner ◽  
Gram Positive ◽  
Concentration Dependent Manner ◽  
Reduced Graphene

Resistance to antimicrobial agents in Gram-positive bacteria has become a major concern in the last decade. Recently, nanoparticles (NP) have emerged as a potential solution to antibiotic resistance. We synthesized three reduced graphene oxide (rGO) nanoparticles, namely rGO, rGO-S, and rGO-S/Se, and characterized them using X-ray diffraction (PXRD), Raman analysis, and thermogravimetric analysis. Transmission electron microscopy confirmed spherical shape nanometer size S and S/Se NPs on the rGO surface. Antibacterial properties of all three nanomaterials were probed against Gram-positive pathogens Staphylococcus aureus and Enterococcus faecalis, using turbidometeric and CFU assays. Among the synthesized nanomaterials, rGO-S/Se exhibited relatively strong antibacterial activity against both Gram-positive microorganism tested in a concentration dependent manner (growth inhibition >90% at 200 μg/mL). Atomic force microscopy of rGO-S/Se treated cells displayed morphological aberrations. Our studies also revealed that rGO composite NPs are able to deposit on the bacterial cell surface, resulting in membrane perturbation and oxidative stress. Taken together, our results suggest a possible three-pronged approach of bacterial cytotoxicity by these graphene-based materials.

scholarly journals 20-HETE increases superoxide production and activates NAPDH oxidase in pulmonary artery endothelial cells

2008 ◽  
Vol 294 (5) ◽  
pp. L902-L911 ◽  
Author(s):  
Meetha Medhora ◽  
Yuenmu Chen ◽  
Stephanie Gruenloh ◽  
Daniel Harland ◽  
Sreedhar Bodiga ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Nadph Oxidase ◽  
Oxidation Products ◽  
Dependent Manner ◽  
Ros Production ◽  
Concentration Dependent Manner ◽  
Physiological Processes ◽  
Contraction And Relaxation ◽  
Endothelial Nitric Oxide

Reactive oxygen species (ROS) signal vital physiological processes including cell growth, angiogenesis, contraction, and relaxation of vascular smooth muscle. Because cytochrome P-450 family 4 (CYP4)/20-hydroxyeicosatetraenoic acid (20-HETE) has been reported to enhance angiogenesis, pulmonary vascular tone, and endothelial nitric oxide synthase function, we explored the potential of this system to stimulate bovine pulmonary artery endothelial cell (BPAEC) ROS production. Our data are the first to demonstrate that 20-HETE increases ROS in BPAECs in a time- and concentration-dependent manner as detected by enhanced fluorescence of oxidation products of dihydroethidium (DHE) and dichlorofluorescein diacetate. An analog of 20-HETE elicits no increase in ROS and blocks 20-HETE-evoked increments in DHE fluorescence, supporting its function as an antagonist. Endothelial cells derived from bovine aortas exhibit enhanced ROS production to 20-HETE quantitatively similar to that of BPAECs. 20-HETE-induced ROS production in BPAECs is blunted by pretreatment with polyethylene-glycolated SOD, apocynin, inhibition of Rac1, and a peptide-based inhibitor of NADPH oxidase subunit p47phox association with gp91. These data support 20-HETE-stimulated, NADPH oxidase-derived, and Rac1/2-dependent ROS production in BPAECs. 20-HETE promotes translocation of p47phox and tyrosine phosphorylation of p47phox in a time-dependent manner as well as increased activated Rac1/2, providing at least three mechanisms through which 20-HETE activates NADPH oxidase. These observations suggest that 20-HETE stimulates ROS production in BPAECs at least in part through activation of NADPH oxidase within minutes of application of the lipid.

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