scholarly journals Human red blood cells express the RNA sensor TLR7 and bind viral RNA

2022 ◽  
Author(s):  
LK Metthew Lam ◽  
Rebecca L. Clements ◽  
Kaitlyn A. Eckart ◽  
Ariel R. Weisman ◽  
Andy E. Vaughan ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Rna Binding ◽  
Protein Band ◽  
Immune Functions ◽  
Red Cell Membrane ◽  
Human Red Blood Cells ◽  
Rbc Membrane ◽  
Human Rbcs

Red blood cells (RBCs) express the nucleic acid-sensing toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs express other nucleic acid-sensing TLRs and bind RNA is unknown. Here we show that human RBCs express the RNA sensor, TLR7. TLR7 is present on the red cell membrane and associates with the RBC membrane protein Band 3. RBCs bind synthetic single-stranded RNA and RNA from pathogenic single-stranded RNA viruses. RNA acquisition by RBCs is attenuated by recombinant TLR7 and inhibitory oligonucleotides. Thus, RBCs may represent a previously unrecognized reservoir for RNA, although how RNA-binding by RBCs modulates the immune response has yet to be elucidated. These findings add to the growing list of non-gas exchanging RBC immune functions.

scholarly journals Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ratnasekhar Ch ◽  
Guillaume Rey ◽  
Sandipan Ray ◽  
Pawan K. Jha ◽  
Paul C. Driscoll ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Mammalian Cells ◽  
Metabolic Flux ◽  
Pentose Phosphate ◽  
Human Red Blood Cells ◽  
Integral Process ◽  
Metabolic Oscillations ◽  
Human Rbcs

AbstractCircadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.

scholarly journals Hemoglobin Oxidation in Stored Blood Accelerates Hemolysis and Oxidative Injury to Red Blood Cells

2020 ◽  
Vol 12 (04) ◽  
pp. 244-249
Author(s):  
Ibrahim Mustafa ◽  
Tameem Ali Qaid Hadwan
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Morphological Changes ◽  
Hemoglobin Concentration ◽  
Red Cell Membrane ◽  
Rbc Membrane ◽  
Hemoglobin Oxidation ◽  
Rbc Indices ◽  
Methemoglobin Formation ◽  
Stored Blood

Abstract Introduction Maintaining blood supply is a challenge in blood banks. Red blood cells (RBCs) stored at 4°C experience issues of biochemical changes due to metabolism of cells, leading to changes collectively referred to as “storage lesions.” Oxidation of the red cell membrane, leading to lysis, contributes to these storage lesions. Methods Blood bags with CPD-SAGM stored at 4°C for 28 days were withdrawn aseptically on days 1, 14, and 28. Hematology analyzer was used to investigate RBC indices. Hemoglobin oxidation was studied through spectrophotometric scan of spectral change. RBC lysis was studied with the help of Drabkin's assay, and morphological changes were observed by light and scan electron microscopy. Results RBCs show progressive changes in morphology echinocytes and spherocytes on day 28. There was 0.85% RBC lysis, an approximately 20% decrease in percentage oxyhemoglobin, and a 14% increase in methemoglobin formation, which shows hemoglobin oxidation on day 28. Conclusions Oxidative damage to RBC, with an increase in storage time was observed in the present study. The observed morphological changes to RBC during the course of increased time shows that there is progressive damage to RBC membrane and a decrease in hemoglobin concentration; percentage RBC lysis is probably due to free hemoglobin and iron.

scholarly journals Bat Red Blood Cells express Nucleic Acid Sensing Receptors and bind RNA and DNA

2022 ◽  
Author(s):  
LK Metthew Lam ◽  
Jane Dobkin ◽  
Kaitlyn A. Eckart ◽  
Ian Gereg ◽  
Andrew DiSalvo ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Red Blood Cells ◽  
Immune Function ◽  
Blood Cells ◽  
Toll Like Receptors ◽  
Cpg Dna ◽  
Human Rbcs ◽  
Insight Into ◽  
Rna And Dna

Red blood cells (RBCs) demonstrate immunomodulatory capabilities through the expression of nucleic acid sensors. Little is known about bat RBCs, and no studies have examined the immune function of bat erythrocytes. Here we show that bat RBCs express the nucleic acid-sensing Toll-like receptors TLR7 and TLR9 and bind the nucleic acid ligands, single-stranded RNA, and CpG DNA. Collectively, these data suggest that, like human RBCs, bat erythrocytes possess immune function and may be reservoirs for nucleic acids. These findings provide unique insight into bat immunity and may uncover potential mechanisms by which virulent pathogens in humans are concealed in bats.

scholarly journals Concanavalin A-mediated binding and sphering of human red blood cells by homologous monocytes.

1976 ◽  
Vol 144 (6) ◽  
pp. 1695-1700 ◽  
Author(s):  
D Guerry ◽  
M A Kenna ◽  
A D Schrieber ◽  
R A Cooper
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Concanavalin A ◽  
Blood Cells ◽  
Human Monocytes ◽  
Blood Monocytes ◽  
Con A ◽  
Peripheral Blood Monocytes ◽  
Human Red Blood Cells ◽  
Human Rbcs

Human red blood cells sensitized with concanavalin A became bound to homologous peripheral blood monocytes. Binding occured at a concentration of 10(5) molecules of tetrameric Con A per red blood cell (RBC) and increased with additional Con A. RBC binding began within 5 min and was maximal at 90 min. Phagocytosis of sensitized RBCs was minimal. RBC attachment was prevented by 0.01 M alpha-methyl-D-mannopyranoside, and, once the RBC-monocyte rosette was established, bound RBCs were largely removed with this specific saccharide inhibitor of Con A. RBCs attached to monocytes became spherocytic and osmotically fragile. The recognition of concanavalin A (Con A)-coated RBCs was not mediated through the monocyte IgG-Fc receptor. These studies demonstrate that, like IgG and C3b, Con A is capable of mediating the binding of human RBCs to human monocytes. Red cells so bound are damaged at the monocyte surface.

Deformation-induced ATP release from red blood cells requires CFTR activity

1998 ◽  
Vol 275 (5) ◽  
pp. H1726-H1732 ◽  
Author(s):  
Randy S. Sprague ◽  
Mary L. Ellsworth ◽  
Alan H. Stephenson ◽  
Mary E. Kleinhenz ◽  
Andrew J. Lonigro
Keyword(s):  
Cystic Fibrosis ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Atp Release ◽  
Chronic Obstructive Lung Disease ◽  
Mechanical Deformation ◽  
Chronic Obstructive ◽  
Healthy Humans ◽  
Human Red Blood Cells ◽  
Human Rbcs

Recently, it was reported that rabbit and human red blood cells (RBCs) release ATP in response to mechanical deformation. Here we investigate the hypothesis that the activity of the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP binding cassette, is required for deformation-induced ATP release from RBCs. Incubation of rabbit RBCs with either of two inhibitors of CFTR activity, glibenclamide (10 μM) or niflumic acid (20 μM), resulted in inhibition of deformation-induced ATP release. To demonstrate the contribution of CFTR to deformation-induced ATP release from human RBCs, cells from healthy humans, patients with cystic fibrosis (CF), or patients with chronic obstructive lung disease (COPD) unrelated to CF were studied. RBCs of healthy humans and COPD patients released ATP in response to mechanical deformation. In contrast, deformation of RBCs from patients with CF did not result in ATP release. We conclude that deformation-induced ATP release from rabbit and human RBCs requires CFTR activity, suggesting a previously unrecognized role for CFTR in the regulation of vascular resistance.

scholarly journals Oxidation of intracellular glutathione after exposure of human red blood cells to hypochlorous acid

1995 ◽  
Vol 307 (1) ◽  
pp. 57-62 ◽  
Author(s):  
M C M Vissers ◽  
C C Winterbourn
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Hypochlorous Acid ◽  
Low Doses ◽  
Red Cell Membrane ◽  
Human Red Blood Cells ◽  
Cell Components ◽  
Slow Infusion ◽  
Higher Doses ◽  
Selective Process

Exposure of human red blood cells to low doses of hypochlorous acid (HOCl) resulted in the loss of intracellular GSH. Oxidation occurred less than 2 min after the addition of HOCl, and required approx. 2.5 mol of HOCl per mol of GSH lost. Loss of GSH preceded oxidation of membrane thiols, the formation of chloramines and haemoglobin oxidation. The susceptibility of intracellular GSH to oxidation by HOCl was two-thirds that of GSH in cell lysates. These results indicate that HOCl can penetrate the red cell membrane, which provides little barrier protection for cytoplasmic components, and that GSH oxidation by HOCl may be a highly selective process. Virtually all of the GSH lost was converted into GSSG. If glucose was added to the medium, most of the GSH oxidized by low doses of HOCl was rapidly regenerated. At higher doses, recovery was less efficient. However, when HOCl was added as a slow infusion rather than in a single bolus, there was increased recovery at higher doses. This indicates that in metabolically active cells regeneration is rapid and GSH may protect cell components from damage by HOCl. HOCl-induced lysis was only slightly delayed by adding glucose to the medium, indicating that lytic injury is not ameliorated by GSH.

scholarly journals Isolation and characterization of an age-related antigen present on senescent human red blood cells

Blood ◽  
1981 ◽  
Vol 58 (2) ◽  
pp. 341-349
Author(s):  
EM Alderman ◽  
HH Fudenberg ◽  
RE Lovins
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Double Immunodiffusion ◽  
Specific Density ◽  
Human Red Blood Cells ◽  
Rbc Membrane ◽  
Isolation And Characterization ◽  
Age Related ◽  
Membrane Bound

Autologous membrane-bound IgG was isolated from a subpopulation of human red blood cells (RBC) with specific density greater than 1.110, by affinity chromatography of purified RBC membrane glycoprotein preparations using immobilized wheat germ agglutinin and immobilized anti-human immunoglobulin (Ig) as immunoabsorbents. The Ig-containing population thus obtained, when further separated by chromatography on Sephadex G-200 in the presence of chaotropic agents, yielded four peaks (Ia, Ib, II, and III). Double immunodiffusion revealed the presence of Ig in the first three peaks (IgM in peak Ia, IgA in Ib, and IgG in II) but not in peak III. Peak III was precipitated by the Ig-containing peaks (Ia, Ib, and II) in immunodiffusion assays, suggesting that the antigenic membrane determinants responsible for the binding of autologous Ig to senescent human RBC were contained in this peak (III). Peaks Ia, Ib and II precipitate purified asialoglycophorin; peak III was reactive with purified autoantibodies directed against asialoglycophorin. These results suggest that an age-related antigenic determinant(s) present on senescent human RBC is exposed by desialylation of the major sialoglycoprotein component of the RBC membrane.

scholarly journals Enrichment of two glycosyl-phosphatidylinositol-anchored proteins, acetylcholinesterase and decay accelerating factor, in vesicles released from human red blood cells

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1481-1485
Author(s):  
P Butikofer ◽  
FA Kuypers ◽  
CM Xu ◽  
DT Chiu ◽  
B Lubin
Keyword(s):  
Cell Membrane ◽  
Blood Cells ◽  
Cell Types ◽  
Gpi Anchor ◽  
Decay Accelerating Factor ◽  
Glycosyl Phosphatidylinositol ◽  
Human Red Blood Cells ◽  
Rbc Membrane ◽  
Human Rbcs

Several proteins are attached to the cell membrane by a glycosyl- phosphatidylinositol (GPI) anchor. In this report, we show that during vesiculation of human RBCs in vitro, two of these proteins, acetylcholinesterase and decay accelerating factor, redistribute on the cell surface and become enriched in the released vesicles. As a result, the remnant cells are depleted of these proteins. We suggest that alterations in the architecture of the RBC membrane that precede vesiculation lead to selective polarization of GPI-anchored proteins within the domain of the membrane destined to become a vesicle. Since vesiculation occurs in many cell types, and if the loss of GPI-anchored proteins accompanies this process, it may have important biologic significance.

scholarly journals Enrichment of two glycosyl-phosphatidylinositol-anchored proteins, acetylcholinesterase and decay accelerating factor, in vesicles released from human red blood cells

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1481-1485 ◽  
Author(s):  
P Butikofer ◽  
FA Kuypers ◽  
CM Xu ◽  
DT Chiu ◽  
B Lubin
Keyword(s):  
Cell Membrane ◽  
Blood Cells ◽  
Cell Types ◽  
Gpi Anchor ◽  
Decay Accelerating Factor ◽  
Glycosyl Phosphatidylinositol ◽  
Human Red Blood Cells ◽  
Rbc Membrane ◽  
Human Rbcs

Abstract Several proteins are attached to the cell membrane by a glycosyl- phosphatidylinositol (GPI) anchor. In this report, we show that during vesiculation of human RBCs in vitro, two of these proteins, acetylcholinesterase and decay accelerating factor, redistribute on the cell surface and become enriched in the released vesicles. As a result, the remnant cells are depleted of these proteins. We suggest that alterations in the architecture of the RBC membrane that precede vesiculation lead to selective polarization of GPI-anchored proteins within the domain of the membrane destined to become a vesicle. Since vesiculation occurs in many cell types, and if the loss of GPI-anchored proteins accompanies this process, it may have important biologic significance.

scholarly journals Human Red Blood Cells as Oxygen Carriers to Improve Ex-Situ Liver Perfusion in a Rat Model

2019 ◽  
Vol 8 (11) ◽  
pp. 1918 ◽  
Author(s):  
Daniele Dondossola ◽  
Alessandro Santini ◽  
Caterina Lonati ◽  
Alberto Zanella ◽  
Riccardo Merighi ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Rat Model ◽  
Blood Cells ◽  
Liver Perfusion ◽  
Small Animal ◽  
Lactate Clearance ◽  
Ex Situ ◽  
Oxygen Carriers ◽  
Human Red Blood Cells ◽  
Human Rbcs

Ex-situ machine perfusion (MP) has been increasingly used to enhance liver quality in different settings. Small animal models can help to implement this procedure. As most normothermic MP (NMP) models employ sub-physiological levels of oxygen delivery (DO2), the aim of this study was to investigate the effectiveness and safety of different DO2, using human red blood cells (RBCs) as oxygen carriers on metabolic recovery in a rat model of NMP. Four experimental groups (n = 5 each) consisted of (1) native (untreated/control), (2) liver static cold storage (SCS) 30 min without NMP, (3) SCS followed by 120 min of NMP with Dulbecco-Modified-Eagle-Medium as perfusate (DMEM), and (4) similar to group 3, but perfusion fluid was added with human RBCs (hematocrit 15%) (BLOOD). Compared to DMEM, the BLOOD group showed increased liver DO2 (p = 0.008) and oxygen consumption ( V O ˙ 2) (p < 0.001); lactate clearance (p < 0.001), potassium (p < 0.001), and glucose (p = 0.029) uptake were enhanced. ATP levels were likewise higher in BLOOD relative to DMEM (p = 0.031). V O ˙ 2 and DO2 were highly correlated (p < 0.001). Consistently, the main metabolic parameters were directly correlated with DO2 and V O ˙ 2. No human RBC related damage was detected. In conclusion, an optimized DO2 significantly reduces hypoxic damage-related effects occurring during NMP. Human RBCs can be safely used as oxygen carriers.

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