scholarly journals Contrasting effects of stored allogeneic red blood cells and their supernatants on permeability and inflammatory responses in human pulmonary endothelial cells

2020 ◽  
Vol 318 (3) ◽  
pp. L533-L548
Author(s):  
Junghyun Kim ◽  
Trang T. T. Nguyen ◽  
Yue Li ◽  
Chen-Ou Zhang ◽  
Boyoung Cha ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Map Kinases ◽  
Inflammatory Responses ◽  
Intercellular Junctions ◽  
Protective Effects ◽  
Pyrin Domain ◽  
Inflammatory Conditions ◽  
Tnf Α ◽  
Rbc Transfusion

Transfusion of red blood cells (RBCs) is a common life-saving clinical practice in severely anemic or hemorrhagic patients; however, it may result in serious pathological complications such as transfusion-related acute lung injury. The factors mediating the deleterious effects of RBC transfusion remain unclear. In this study, we tested the effects of washed long-term (RBC-O; >28 days) versus short-term (RBC-F; <14 days) stored RBCs and their supernatants on lung endothelial (EC) permeability under control and inflammatory conditions. RBCs enhanced basal EC barrier function as evidenced by an increase in transendothelial electrical resistance and decrease in permeability for macromolecules. RBCs also attenuated EC hyperpermeability and suppressed secretion of EC adhesion molecule ICAM-1 and proinflammatory cytokine IL-8 in response to LPS or TNF-α. In both settings, RBC-F had slightly higher barrier protective effects as compared with RBC-O. In contrast, supernatants from both RBC-F and RBC-O disrupted the EC barrier. The early phase of EC permeability response caused by RBC supernatants was partially suppressed by antioxidant N-acetyl cysteine and inhibitor of Src kinase family PP2, while addition of heme blocker and inhibition of NOD-like receptor family pyrin domain containing protein 3 (NLRP3), stress MAP kinases, receptor for advanced glycation end-products (RAGE), or Toll-like receptor-4 (TLR4) signaling were without effect. Morphological analysis revealed that RBC supernatants increased LPS- and TNF-α-induced breakdown of intercellular junctions and formation of paracellular gaps. RBC supernatants augmented LPS- and TNF-α-induced EC inflammation reflected by increased production of IL-6, IL-8, and soluble ICAM-1. These findings demonstrate the deleterious effects of RBC supernatants on EC function, which may have a major impact in pathological consequences associated with RBC transfusion.

Redox imbalance of red blood cells impacts T lymphocyte homeostasis: implication in carotid atherosclerosis

2011 ◽  
Vol 106 (12) ◽  
pp. 1117-1126. ◽  
Author(s):  
Brigitta Buttari ◽  
Linda Petrone ◽  
Elisabetta Straface ◽  
Lucrezia Gambardella ◽  
Donatella Pietraforte ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Healthy Subjects ◽  
Carotid Atherosclerosis ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Activated T Lymphocytes

SummaryOxidative stress and immune/inflammatory responses are key pathogenetic factors of atherosclerotic disease. In this contest, mechanisms that regulate survival and death of immune cells may be relevant. Previous studies have demonstrated that red blood cells (RBCs) are physiologically able to inhibit apoptosis and to promote proliferation of activated T lymphocytes from healthy subjects. The aim of the present study was to evaluate whether RBCs from patients with carotid atherosclerosis maintain their property to modulate T cell homeostasis. Peripheral blood lymphocytes (PBLs) obtained from healthy subjects were activated in vitro by phytohemagglutinin in the presence/absence of RBCs from patients with carotid atherosclerosis or of in vitro oxidised RBCs from healthy subjects. Levels of reactive oxygen species (ROS) and aging markers of RBCs as well as susceptibility to apoptosis of PBLs were evaluated by flow cytometry. PBL proliferation was evaluated by 3H-methyl-thymidine incorporation assay whereas secretion of cytokines, analysed in view of their key role in T cell function, was assessed by ELISA. Levels of ROS and phosphatidyl-serine externalisation, a sign of RBC aging, resulted significantly higher in RBCs from patients than in those from healthy subjects, whereas surface glycophorin A expression and reduced glutathione content did the opposite. Unlike RBCs obtained from healthy subjects, RBCs from patients and in vitro oxidised RBCs did not protect activated T lymphocytes from apoptosis. Hence, RBCs from patients with carotid atherosclerosis, probably due to their oxidative imbalance, impact T cell integrity and function. Our results suggest a new regulatory role for RBCs in atherosclerosis.

scholarly journals Synthesis and Antioxidant of Some New Pyrazolo[1,5-a]pyrimidine, Pyrazolo[5,1-b]quinazoline and Imidazo[1,2-b]pyrazole Derivatives Incorporating Phenylsulfonyl Moiety

2021 ◽  
Vol 10 (3) ◽  
pp. 2414-2428
Keyword(s):  
Antioxidant Activity ◽  
Free Radical ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Protective Effects ◽  
Oxidative Hemolysis ◽  
Elemental Analyses ◽  
Phenolic Group ◽  
High Antioxidant Activity ◽  
New Compounds

The synthesis and antioxidant of some new pyrazole analogs were described. It is achieved by the reaction of phenyl-4-(phenylsulfonyl)-1H-pyrazole-3,5-diamine (3) with different bifunctional reagents. The free radical-induced damage and the protective effects of the newly synthesized pyrazoles were studied. These new compounds inhibit the free radical-induced oxidative hemolysis of red blood cells effectively. It was found that these compounds effectively inhibit the free radical-induced oxidative hemolysis of red blood cells. Compound 5, which contain phenolic group, and 17, which bear sulfur, nitrogen atoms, and benzothiazole ring, respectively displayed high antioxidant activity. Analogs 15, 11, 10, and 9 were proved to exhibit antioxidative activity. Structures of new pyrazoles were confirmed by spectroscopic and elemental analyses and have been screened for their antioxidant activity.

Protective Effects of Resveratrol and its Analogues against Free Radical-Induced Oxidative Hemolysis of Red Blood Cells†

2010 ◽  
Vol 20 (11) ◽  
pp. 1313-1318 ◽  
Author(s):  
Jian-Guo Fang ◽  
Man Lu ◽  
Lan-Ping Ma ◽  
Li Yang ◽  
Long-Min Wu ◽  
...  
Keyword(s):  
Free Radical ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Protective Effects ◽  
Oxidative Hemolysis

Opposite effects of tumor necrosis factor and soluble fibronectin on junctional adhesion molecule-A in endothelial cells

2005 ◽  
Vol 288 (6) ◽  
pp. L1081-L1088 ◽  
Author(s):  
Ofelia M. Martinez-Estrada ◽  
Luca Manzi ◽  
Paolo Tonetti ◽  
Elisabetta Dejana ◽  
Gianfranco Bazzoni
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Surface ◽  
Adhesion Molecule ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Intercellular Junctions ◽  
Facs Analysis ◽  
Edema Formation ◽  
Inflammatory Conditions ◽  
Necrosis Factor

Junctional adhesion molecule-A (JAM-A) regulates key inflammatory responses, such as edema formation and leukocyte transmigration. Although it has been reported that the inflammatory cytokine tumor necrosis factor (TNF) causes the disassembly of JAM-A from the intercellular junctions, the mechanism has not been elucidated fully. Here, we report that TNF enhances the solubility of JAM-A in Triton X-100 and increases the amount of Triton-soluble JAM-A dimers at the cell surface but does not change the total levels of cellular JAM-A. Thus we hypothesized that TNF causes the redistribution of JAM-A from the junctions to the cell surface and that junction disassembly is sufficient to account for JAM-A redistribution. Intriguingly, however, even after complete disassembly of the junctions (with EDTA and trypsin), higher levels of JAM-A are detectable at the cell surface (by FACS analysis) in cells that had been previously incubated in the presence of TNF than in its absence. Thus we propose that TNF causes not only the disassembly of JAM-A from the junctions and its subsequent redistribution to the cell surface but also its dispersal in such a way that JAM-A becomes more easily accessible to the antibodies used for FACS analysis. Finally, we evaluated whether soluble fibronectin might attenuate the effects of TNF on JAM-A, as some inflammatory conditions are associated with the depletion of plasma fibronectin. We found that fibronectin reduces the effect of TNF on the disassembly of JAM-A, but not on its dispersal, thus further stressing that disassembly and dispersal can be functionally dissociated.

Effects of Pan-Selectin Antagonist GMI-1070 on the Treatment of Vaso-Occlusion in Sickle Cell Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 535-535 ◽  
Author(s):  
Jungshan Chang ◽  
John T Patton ◽  
Paul S. Frenette ◽  
John L. Magnani
Keyword(s):  
Blood Flow ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Small Molecule ◽  
Vascular Endothelium ◽  
Intravital Microscopy ◽  
Blood Cells ◽  
Tnf Α ◽  
Sickle Red Blood Cells ◽  
Adherent Leukocytes

Abstract Acute vaso-occlusion (VOC) in patients with sickle cell disease (SCD) induces intense pain arising from organ damage and is the major cause of morbidity and mortality. Hypoxia and abnormal sickle red blood cells (RBC) induce inflammatory mediators and activation of the vascular endothelium leading to the recruitment of adherent leukocytes and sickle RBC followed by aggregates that eventually occlude blood flow. Previous studies have implicated the critical roles of cell adhesion molecules E- and P-selectins by using intravital microscopy in SCD mice (Berkeley strain) with altered genetic backgrounds (SCD transplanted in recipients lacking E-and P-selectins), or antibodies against endothelial selectins, or small molecules directed against the selectins. Here, we designed a treatment protocol for this SCD mouse model, in which a small molecule pan-selectin antagonist (GMI-1070) is administered to sickle cell mice late in the process of established vaso-occlusion in order to test the effects of GMI-1070 in a more clinically relevant model. GMI-1070 is a small molecule pan-selectin antagonist designed on the bioactive conformation of the carbohydrate ligand and inhibits leukocyte adhesion to activated endothelium in vitro with particularly strong activity against E-selectin (IC50 = 3.4 μM). Berkeley SCD mice were generated by bone marrow transplantation into lethally irradiated C57BL/6 male mice and the fully engrafted (100% donor RBC chimerism) mice were used for intravital microscopy experiments. VOC events were induced by injection with TNF-α at time 0 and the formation of occlusions were allowed to proceed as long as possible just prior to the death of the control mice. GMI-1070 (20 mg/kg) or vehicle (PBS pH 7.4) were administered at t = 110 min. Post-capillary and collecting venules in the cremaster muscle were analyzed for effects on an established VOC event. Under these conditions, GMI-1070 significantly increased the microcirculatory blood flow to levels observed in non-sickle cell mice (vehicle: 237 ± 15 nL/sec; GMI-1070: 533 ± 58 nL/sec; p&lt;0.0001). The recruitment of adherent leukocytes to the vascular endothelium was also significantly reduced (vehicle: 2235 ± 156; GMI-1070: 1270 ± 203 cells/mm2; p=0.0013), and there were significant and dramatic reductions in the capture of sickle red blood cells to adherent leukocytes (vehicle: 0.68 ± 0.27; GMI-1070: 0.03 ± 0.01 interactions/WBC, min, 100ml; p=0.0003). Mice began to succumb to VOC within 2.5 hours after injection of TNF-α and surgical trauma which continued until all of the control SCD mice died. Administration of GMI-1070 prevented the death of half of the treated mice within the timeframe of the experiment and extended the median survival of mice from 5 hours (control, vehicle-treated) to greater than 9 hours for the GMI-1070- treated SCD mice (p = 0.0067). These studies show that GMI-1070 can significantly and dramatically improve the condition and survival of the animals with a severe VOC even when dosed well after the initiating challenge. Thus these data strongly support the use of GMI-1070 for the treatment of patients in acute vaso-occlusive crisis. GMI-1070 is currently in a Phase I clinical trial.

scholarly journals Quality of Red Blood Cells Isolated from Umbilical Cord Blood Stored at Room Temperature

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Mariia Zhurova ◽  
John Akabutu ◽  
Jason Acker
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Red Blood Cells ◽  
Future Development ◽  
Blood Cells ◽  
Room Temperature ◽  
Fetal Hemoglobin ◽  
Blood Characteristics ◽  
Rbc Transfusion

Red blood cells (RBCs) from cord blood contain fetal hemoglobin that is predominant in newborns and, therefore, may be more appropriate for neonatal transfusions than currently transfused adult RBCs. Post-collection, cord blood can be stored at room temperature for several days before it is processed for stem cells isolation, with little known about how these conditions affect currently discarded RBCs. The present study examined the effect of the duration cord blood spent at room temperature and other cord blood characteristics on cord RBC quality. RBCs were tested immediately after their isolation from cord blood using a broad panel of quality assays. No significant decrease in cord RBC quality was observed during the first 65 hours of storage at room temperature. The ratio of cord blood to anticoagulant was associated with RBC quality and needs to be optimized in future. This knowledge will assist in future development of cord RBC transfusion product.

Protective effects of flavonols and their glycosides against free radical-induced oxidative hemolysis of red blood cells

Life Sciences ◽  
2006 ◽  
Vol 78 (21) ◽  
pp. 2488-2493 ◽  
Author(s):  
Fang Dai ◽  
Qing Miao ◽  
Bo Zhou ◽  
Li Yang ◽  
Zhong-Li Liu
Keyword(s):  
Free Radical ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Protective Effects ◽  
Oxidative Hemolysis
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