Article
Multidisciplinary Sciences
Marijke Grau, Lennart Kuck
Summary: Antibody labeling of RBC proteins is a commonly used method to detect protein content changes and acute alterations in protein activation states. It has various applications in assessing RBC treatments, characterizing disease states, and describing cellular coherencies.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Medicine, General & Internal
Julie Vanderelst, Alexandre Rousseau, Nicolas Selvais, Patrick Biston, Karim Zouaoui Boudjeltia, Michael Piagnerelli
Summary: The study found that during sepsis, there are changes in the shape and deformability of red blood cells, as well as a decrease in the expression of the CD35 membrane protein. These changes may contribute to the phagocytosis of red blood cells and the development of anemia in sepsis.
FRONTIERS IN MEDICINE
(2022)
Article
Biology
Marijke Grau, Lennart Kuck, Thomas Dietz, Wilhelm Bloch, Michael J. Simmonds
Summary: Red blood cell (RBC) deformability is crucial for microcirculatory function and is enhanced by physiological shear stress while negatively affected by supraphysiological shears and/or free radical exposure. Older RBCs demonstrate lower deformability compared to younger RBCs, and both sub-populations experience decreased deformability due to free radicals. Shear exposure does not impact reactive species in the sub-populations, but it reduces nitric oxide synthase (NOS) activation and increases RBC deformability in older RBCs. These findings reveal the complex interplay between mechanical stress, free radicals, and RBC mechanics in different sub-populations.
Article
Cardiac & Cardiovascular Systems
Francesca Leo, Tatsiana Suvorava, Sophia K. Heuser, Junjie Li, Anthea LoBue, Frederik Barbarino, Eugenia Piragine, Rebekka Schneckmann, Beate Hutzler, Miranda E. Good, Bernadette O. Fernandez, Lukas Vornholz, Stephen Rogers, Allan Doctor, Maria Grandoch, Johannes Stegbauer, Eddie Weitzberg, Martin Feelisch, Jon O. Lundberg, Brant E. Isakson, Malte Kelm, Miriam M. Cortese-Krott
Summary: This study demonstrates that eNOS in ECs and RBCs independently contribute to blood pressure homeostasis. EC eNOS KO mice exhibited significantly impaired aortic dilatory responses to acetylcholine, loss of flow-mediated dilation, and increased blood pressure. On the other hand, RBC eNOS KO mice showed no alterations in acetylcholine-mediated dilation or flow-mediated dilation but were hypertensive.
Review
Biochemistry & Molecular Biology
Jun Kobayashi, Kazuo Ohtake, Isamu Murata, Kunihiro Sonoda
Summary: The rheological properties of red blood cells (RBCs) are important for their microcirculation. Lifestyle-related diseases can lead to decreased RBC deformability, which is associated with increased oxidative stress and decreased nitric oxide (NO) bioavailability. NO can protect RBC membrane flexibility by shielding redox-sensitive cysteine residues. Nitrate-rich diets and moderate exercise can enhance NO production and increase RBC deformability. This review focuses on the molecular mechanism of NO generation and its prophylactic effects against decreased RBC deformability in lifestyle-related diseases.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2022)
Article
Cell Biology
Marijke Grau, Lars Ibershoff, Jonas Zacher, Janina Bros, Fabian Tomschi, Katharina Felicitas Diebold, Hans-Georg Predel, Wilhelm Bloch
Summary: Infection with SARS-CoV-2 might lead to alterations in the morphology and rheological parameters of red blood cells, affecting oxygen supply. This study found that individuals with mild COVID-19 exhibited changes in the shape and deformability of red blood cells, which may be related to altered hematological parameters and increased RBC-NOS activation.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Travis Nemkov, Sarah C. Skinner, Elie Nader, Davide Stefanoni, Melanie Robert, Francesca Cendali, Emeric Stauffer, Agnes Cibiel, Camille Boisson, Philippe Connes, Angelo D'Alessandro
Summary: A controlled, high-intensity cycling test resulted in decreased RBC deformability, increased microparticle generation, oxidative stress, and activation of membrane lipid remodeling mechanisms. Metabolites involved in CoA synthesis and carnitine conversion were significantly correlated with RBC properties during exercise.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Miriam M. Cortese-Krott, Tatsiana Suvorava, Francesca Leo, Sophia K. Heuser, Anthea LoBue, Junjie Li, Stefanie Becher, Rebekka Schneckmann, Tanu Srivrastava, Ralf Erkens, Georg Wolff, Joachim P. Schmitt, Maria Grandoch, Jon O. Lundberg, John Pernow, Brant E. Isakson, Eddie Weitzberg, Malte Kelm
Summary: This study reveals that red blood cell endothelial nitric oxide synthase (RBC eNOS) plays a role in limiting infarct size in acute myocardial infarction (AMI) and regulates coronary blood flow and cardiac function. These findings suggest that RBC eNOS signaling may represent a novel target for interventions in ischemia/reperfusion after myocardial infarction.
Article
Biochemistry & Molecular Biology
Silvie Suriany, Iris Xu, Honglei Liu, Pinar Ulker, G. Esteban Fernandez, Richard Sposto, Matthew Borzage, Rosalinda Wenby, Herbert J. Meiselman, Henry Jay Forman, Thomas D. Coates, Jon A. Detterich
Summary: Sickle cell anemia patients exhibit increased basal nitric oxide (NO·) production in RBCs, with morphological changes during shear stress. NO· production is influenced by NOS, and sickle-shaped RBCs with inclusions show higher NO· production during shear.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Tamir Tsohar, Shaul Beyth, Alexander Gural, Dan Arbell, Saul Yedgar, Gregory Barshtein
Summary: This study investigated the impact of non-physiological mechanical stress during surgery on red blood cell deformability. The findings showed that mechanical stress reduces cell deformability, increases the percentage of undeformable cells, and leads to hemolysis of rigid cells. The final outcome depends on the initial concentration of undeformable cells in the sample.
APPLIED SCIENCES-BASEL
(2022)
Article
Physiology
Michael Piagnerelli, Julie Vanderelst, Alexandre Rousseau, Daniel Monteyne, David Perez-Morga, Patrick Biston, Karim Zouaoui Boudjeltia
Summary: In patients with severe hypoxemic COVID-19, red blood cells (RBCs) showed normal deformability on admission, which remained unchanged over the first week despite changes in shape. This maintenance of normal RBC deformability may contribute to the adequate microcirculatory response to severe hypoxia observed in these patients.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Physiology
Perumal Thiagarajan, Charles J. Parker, Josef T. Prchal
Summary: Normal human red blood cells have an average life span of about 120 days in the circulation before being engulfed by macrophages. The exact molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains unclear despite numerous investigations. Changes in red cell physicochemical properties as they age have been proposed as recognition tags for macrophages, but their causal role in red cell clearance has not been established.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Julian Eder, Leonie Schumm, Jakob P. P. Armann, Milo A. A. Puhan, Felix Beuschlein, Clemens Kirschbaum, Reinhard Berner, Nicole Toepfner
Summary: This study investigated the morphological and mechanical characteristics of red blood cells (RBCs) after SARS-CoV-2 infection in children and adolescents using real-time deformability-cytometry (RT-DC), and explored the relationship between RBC alterations and the clinical course of COVID-19. The results showed that the median RBC deformation was significantly increased in SARS-CoV-2-seropositive children and adolescents until 6 months post-COVID-19, indicating a mild course of the disease.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Beata Csiszar, Gergely Galos, Simone Funke, Dora Kinga Kevey, Matyas Meggyes, Laszlo Szereday, Peter Kenyeres, Kalman Toth, Barbara Sandor
Summary: Our study investigated the maternal red blood cell properties in early-onset preeclampsia. We found that RBC aggregation was significantly elevated and RBC deformability reduced in women with PE. The AI and M index values showed potential for predicting early-onset PE, with a positive linear relationship observed between AI and gestational age at birth.
Article
Multidisciplinary Sciences
Saman Ebrahimi, Prosenjit Bagchi
Summary: This study investigates the influence of reduced red blood cell (RBC) deformability on microvascular hemodynamics using a high-fidelity, 3D computational model. The results predict significant and heterogeneous changes in RBC trafficking, hematocrit, vascular resistance, and wall shear stress. The study elucidates the cellular-scale mechanisms leading to these changes and suggests that they may contribute to morphological abnormalities in capillary vessel networks observed in diseases.
SCIENTIFIC REPORTS
(2022)
Article
Rheumatology
Ronald F. van Vollenhoven, Bevra H. Hahn, George C. Tsokos, Peter Lipsky, Robert M. Gordon, Kaiyin Fei, Kim Hung Lo, Marc Chevrier, Shawn Rose, Pamela Berry, Zhenling Yao, Chetan S. Karyekar, Qing Zuraw
Summary: The long-term efficacy and safety of ustekinumab in patients with active systemic lupus erythematosus was evaluated through a 2-year study. The results showed that ustekinumab led to clinical improvements in global and organ-specific SLE activity measures, with no new or unexpected safety concerns.
JOURNAL OF RHEUMATOLOGY
(2022)
Editorial Material
Rheumatology
Afroditi Boulougoura, George C. Tsokos
Summary: Although there are numerous interconnected pathways involved in the development of systemic lupus erythematosus (SLE), each pathway dominates only a fraction of patients. This complexity contributes to the limited clinical benefit observed in SLE clinical trials, including those testing iberdomide.
NATURE REVIEWS RHEUMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Dalia L. Lezzar, Fong W. Lam, Ravin Huerta, Anton Mukhamedshin, Madeleine Lu, Sergey S. Shevkoplyas
Summary: This study introduces a novel high-throughput microfluidic device based on controlled incremental filtration technology for efficient leukapheresis. Compared to traditional centrifugation-based separation, the device has a smaller void volume, faster separation speed, and fewer platelet losses, with no measurable damage to red blood cells. The study demonstrates for the first time the highly efficient separation of cells from recirculating blood using a microfluidic device, indicating the feasibility of centrifugation-free, low-ECV leukapheresis using high-throughput microfluidic cell separation technology. This capability would be particularly useful for underserved young children.
SCIENTIFIC REPORTS
(2022)
Article
Hematology
Matthew S. Karafin, Joshua J. Field, Anton Ilich, Lang Li, Bahjat F. Qaquish, Sergey S. Shevkoplyas, Tatsuro Yoshida
Summary: This study found that plasma from SCD patients during crisis may affect the functionality of donor red blood cells, while hypoxic storage can preserve their deformability and reduce hemolysis. This has important implications for improving transfusion efficacy.
Correction
Multidisciplinary Sciences
Hui Xia, Briony C. Strachan, Sean C. Gifford, Sergey S. Shevkoplyas
SCIENTIFIC REPORTS
(2022)
Article
Biochemical Research Methods
Kumar Abhishek, Anto Sam Crosslee Louis Sam Titus, Mai T. P. Dinh, Anton Mukhamedshin, Chandra Mohan, Sean C. Gifford, Sergey S. Shevkoplyas
Summary: This study describes a new approach that enables the size-based separation of desired lymphocyte subsets by artificially enlarging unwanted lymphocytes and other blood cells. The new rosette-enabled size-based (RESIZE) separation approach is faster and more efficient than the standard immunodensity method, with similar recovery rates but higher purity for lymphocyte subsets. The integration of RESIZE into the manufacturing workflow of cellular immunotherapies could greatly streamline the process and improve their cost and availability.
Article
Multidisciplinary Sciences
Marc Scherlinger, Wenliang Pan, Ryo Hisada, Afroditi Boulougoura, Nobuya Yoshida, Milena Vukelic, Masataka Umeda, Suzanne Krishfield, Maria G. Tsokos, George C. Tsokos
Summary: This study reveals the defective metabolism and function of Treg cells in systemic lupus erythematosus (SLE) and identifies CaMK4 and PFKP as key regulators. Targeting CaMK4 and PFKP holds promise for restoring Treg cell function and improving disease outcomes in SLE patients.
Review
Immunology
Kumar Abhishek, Malavika Nidhi, Srinandhini Chandran, Sergey S. Shevkoplyas, Chandra Mohan
Summary: Regulatory T cells (Tregs) are a type of lymphocyte that regulate the immune system by suppressing unwanted immune responses, preventing autoimmune diseases and inappropriate inflammatory reactions. They have shown promise in preventing graft vs. host disease, alleviating autoimmune symptoms, and promoting transplant tolerance. This review provides an overview of Treg cells, including important markers and subsets, as well as the methodology used for manufacturing adoptive regulatory T cell therapies (TRACT). The approaches and outcomes of several clinical trials involving adoptive transfer of Tregs to patients are also discussed.
CLINICAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Austin H. Routt, Natalia Yang, Nathaniel Z. Piety, Madeleine Lu, Sergey S. Shevkoplyas
Summary: We developed a highly accurate open-source method for classifying the morphology of red blood cells (RBCs) based on deep learning. The method allows for easy use in research and clinical applications and revealed insights into the degradation of RBC functional properties during hypothermic storage.
SCIENTIFIC REPORTS
(2023)
Correction
Immunology
Marc Scherlinger, Christophe Richez, George C. Tsokos, Eric Boilard, Patrick Blanco
NATURE REVIEWS IMMUNOLOGY
(2023)
Review
Immunology
Marc Scherlinger, Christophe Richez, George C. C. Tsokos, Eric Boilard, Patrick Blanco
Summary: Immune-mediated inflammatory diseases (IMIDs) are characterized by excessive and uncontrolled inflammation and thrombosis, both of which are responsible for organ damage, morbidity and death. Platelets play a central role in the pathogenesis and progression of IMIDs, as they are activated by disease-specific factors and promote inflammation and tissue injury. Targeting platelet activation and their interaction with the immune system are promising therapeutic strategies in IMIDs.
NATURE REVIEWS IMMUNOLOGY
(2023)
Correction
Urology & Nephrology
George C. Tsokos, Afroditi Boulougoura, Vivek Kasinath, Yushiro Endo, Reza Abdi, Hao Li
NATURE REVIEWS NEPHROLOGY
(2023)
Review
Urology & Nephrology
George C. Tsokos, Afroditi Boulougoura, Vivek Kasinath, Ushiro Endo, Reza Abdi, Hao Li
Summary: The immune cells and parenchymal cells in the kidney play a significant role in the induction of kidney damage. Kidney parenchymal cells provide structural immunity to the kidney through the regulation of immune-relevant processes, affecting kidney inflammation and injury. Targeted drug delivery to kidney parenchymal cells holds promise for preventing or reversing inflammation in specific forms of kidney injury and disease.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Immunology
Wenliang Pan, Marc Scherlinger, Nobuya Yoshida, Maria G. Tsokos, George C. Tsokos
Summary: This study demonstrates that PPP2R2D, a regulatory subunit of protein phosphatase 2A, acts as a negative regulator of immune checkpoint receptors. Its absence exacerbates effector T cell exhaustion and promotes regulatory T cell expansion. The expression levels of PPP2R2D are positively correlated with the infiltration of immune cells in melanoma patients.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Ryo Hisada, Nobuya Yoshida, Masataka Umeda, Catalina Burbano, Rhea Bhargava, Marc Scherlinger, Michihito Kono, Vasileios C. Kyttaris, Suzanne Krishfield, George C. Tsokos
Summary: SIRT2 suppresses IL-2 production and promotes Th17 cell differentiation, which contributes to the pathogenesis of SLE. SIRT2 activates the mTORC1/HIF-1α/RORγt pathway by deacetylating p70S6K, initiating Th17 cell differentiation. Overexpression of SIRT2 is found in SLE patients, suggesting that SIRT2 may be a potential therapeutic target for SLE.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)