Physical phenotype of blood cells is altered in COVID-19

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by rapid spreading and high mortality worldwide. While the pathology is not yet fully understood, hyper-inflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than 4 million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in erythrocyte deformability, lymphocyte stiffness, monocyte size, and neutrophil size and deformability. While some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.

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Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

International Journal of Molecular Sciences ◽

10.3390/ijms22073649 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3649

Author(s):

Patricia Ramos-Ramírez ◽

Omar Tliba

Keyword(s):

Current Knowledge ◽

Inflammatory Diseases ◽

Cell Communication ◽

Cell Types ◽

The Body ◽

Dominant Negative ◽

Negative Effects ◽

Independent Manner ◽

Distinct Cell ◽

Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

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Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

10.1101/2021.10.11.463714 ◽

2021 ◽

Author(s):

Andrew D. Beale ◽

Priya Crosby ◽

Utham K. Valekunja ◽

Rachel S. Edgar ◽

Johanna E. Chesham ◽

...

Keyword(s):

Circadian Rhythms ◽

Red Blood Cells ◽

Blood Cells ◽

Human Subjects ◽

Developmental Regulation ◽

Physiological Role ◽

Cell Types ◽

The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

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Gut Microbiome and Organ Fibrosis

Nutrients ◽

10.3390/nu14020352 ◽

2022 ◽

Vol 14 (2) ◽

pp. 352

Author(s):

Carolina F. F. A. Costa ◽

Benedita Sampaio-Maia ◽

Ricardo Araujo ◽

Diana S. Nascimento ◽

Joana Ferreira-Gomes ◽

...

Keyword(s):

Gut Microbiome ◽

Inflammatory Diseases ◽

Adaptive Immune System ◽

Organ Damage ◽

Pathological Process ◽

The Body ◽

Intestinal Fibrosis ◽

Immune Mediated ◽

Major Player ◽

Organ Fibrosis

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.

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Biomarkers and recent advances in the management and therapy of sickle cell disease

F1000Research ◽

10.12688/f1000research.6615.1 ◽

2015 ◽

Vol 4 ◽

pp. 1050 ◽

Cited By ~ 2

Author(s):

Marilyn J. Telen

Keyword(s):

Sickle Cell Disease ◽

Red Blood Cells ◽

Sickle Cell ◽

Blood Cells ◽

Genetic Defect ◽

Organ Damage ◽

The Body ◽

Cell Disease ◽

Modern Health Care ◽

Vaccine Prophylaxis

Although production of hemoglobin S, the genetic defect that causes sickle cell disease (SCD), directly affects only red blood cells, the manifestations of SCD are pervasive, and almost every cell type and organ system in the body can be involved. Today, the vast majority of patients with SCD who receive modern health care reach adulthood thanks to vaccine prophylaxis and improvements in supportive care, including transfusion. However, once patients reach adulthood, they commonly experience recurrent painful vaso-occlusive crises and frequently have widespread end-organ damage and severely shortened life expectancies. Over the last several decades, research has elucidated many of the mechanisms whereby abnormal red blood cells produce such ubiquitous organ damage. With these discoveries have come new ways to measure disease activity. In addition, new pharmaceutical interventions are now being developed to address what has been learned about disease mechanisms.

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Continued blood cell formation in spherical bodies in a long-term mouse spleen culture

Blood ◽

10.1182/blood.v77.6.1211.bloodjournal7761211 ◽

1991 ◽

Vol 77 (6) ◽

pp. 1211-1217

Author(s):

Y Matsuya ◽

N Yanai ◽

H Ohtani ◽

H Naganuma ◽

M Obinata

Keyword(s):

Blood Cell ◽

Cell Formation ◽

Three Dimensional ◽

Cell Types ◽

Spherical Body ◽

The Body ◽

Dimensional Structure ◽

Newborn Mice ◽

Prolonged Culture

During the primary culture of spleen fragments of newborn mice, a spherical body (d = circa 200 to 300 microns) as a three-dimensional cellular organization was formed. Continued production of blood cells from the spherical body was observed without changing its size for about 2 months of culture. Without growth factor, the spherical bodies produced mainly lymphocytes and macrophages. Addition of interleukin-3 enhanced their granulocyte formation, and this enhancement was observed even after a prolonged maintenance without growth factors. The spherical bodies were composed of a uniform mixture of endothelial cells and fibroblasts within the body, and cell-cell contacts between lymphocytes and fibroblasts were notable in the periphery. With prolonged culture, the spherical bodies showed a definite change in their structure by sorting two cell types and the blood cell production gradually decreased. These results suggested that a three-dimensional structure was required for the maintenance, growth, and differentiation of blood cell progenitors in the long-term spleen culture.

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1. What are stem cells?

10.1093/actrade/9780198869290.003.0001 ◽

2021 ◽

pp. 1-18

Author(s):

Jonathan Slack

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Structural Unit ◽

Embryonic Stem ◽

Cell Types ◽

The Body ◽

Differentiated Cells ◽

Mammalian Embryos ◽

A Cell

‘What are stem cells?’ explains that a stem cell is a cell that can both reproduce itself and generate offspring of different functional cell types and begins by considering the nature of cells in general, wherein cells are understood to be the ultimate structural unit of an animal or plant body. Stem cells in the body persist long term, usually for the lifetime of the organism. Good examples of differentiated cells arising from stem cells are those of the skin, the blood, and the lining of the intestine. Embryonic stem cells are grown in culture from early mammalian embryos. The reason that stem cell research is seen as the source for new cures is largely because this technology offers a route to cell therapy.

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A “strange” case of COPD

Clinical Management Issues ◽

10.7175/cmi.v4i3s.1156 ◽

2015 ◽

Vol 4 (3S) ◽

pp. 63-66

Author(s):

Laura Massarelli ◽

Valerio Tomaselli ◽

Carlo Bussolino ◽

Valter Saracco

Keyword(s):

Celiac Disease ◽

Respiratory Tract ◽

Bacterial Infections ◽

B Lymphocyte ◽

Inflammatory Diseases ◽

Organ Damage ◽

Positive Influence ◽

Lymphoid Organ ◽

The Body ◽

Recurrent Infections

Common variable immunodeficiency (CVID) is a rare syndrome, characterized by hypogammaglobulinemia and limited antibody responses due to either impaired B-lymphocyte development or B-cell responses to T-lymphocyte signals. CVID is frequently associated with bacterial infections, particularly against respiratory tract, that could determine a permanent organ damage (COPD, asthma), increased incidence of both autoimmune diseases and cancer, high prevalence of gastrointestinal inflammatory diseases (ulcerative colitis, Crohn’s disease, celiac disease), lymphoproliferative and granulomatous diseases. Given that the gastrointestinal tract is the largest lymphoid organ in the body, it’s not surprising that intestinal diseases are common in immunodeficiency. CVID is considered a congenital condition but it is usually diagnosed in adulthood. We describe the case of a 43-year-old man affected by recurrent infections of respiratory tract with CVID, celiac disease and type 1 diabetes. With the exclusion of gluten from the diet, patient achieved an improvement of serum level of immunoglobulins and a reduction of recurrent infections. This fact suggests that the interruption of the gluten stimulus could have a positive influence on the other diseases, improving the metabolic compensation and stabilizing the immune system.

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Structural analysis of morphometric and morphofunctional state of immunocompetent blood cells in case of purulent-inflammatory diseases of soft tissues on the background of type 2 diabetes

Modern medical technologies ◽

10.34287/mmt.2(41).2019.14 ◽

2019 ◽

Vol 41 part 1 (2) ◽

pp. 71-76

Author(s):

M. D. Zheliba ◽

M. G. Bogachyuk ◽

M. I. Pokidko ◽

S. D. Khimich

Keyword(s):

Type 2 Diabetes ◽

Immune System ◽

Blood Cells ◽

Soft Tissues ◽

Inflammatory Diseases ◽

Immune Defense ◽

The Body ◽

Neutrophil Granulocytes ◽

Study Results

Relevance. According to the study’s results, steady changes in various parts of the immune system: cellular, humeral, phagocytic activity is revealed in patients with type 2 diabetes. Hyperglycemia, hyperlipidemia, insulin resistance, and adaptive ehyperinsulinemia affect the cells of the immune system, promoting the development of metabolic immunosuppressant and forming a stable immunological disorder. The purpose of the study into the morphometric and morphofunctional state of peripheral blood leukocytes in patients with type 2 diabetes to determine their significance in the development of purulent-inflammatory diseases of soft tissues are research. Materials and methods. In this work, the analysis of morphometric, cytogystochemical and laboratory study results of the control (20 healthy volunteers) and thematic (47 patients with supportive soft tissue disease son the background of type 2 diabetes mellitus) study groups with the statistical processing of the obtained results was used. Results. The investigation of morphofunctional features of nonspecific and specific protection cells for purulent inflammatory diseases of tissues on the background of type 2 diabetes showed that the basis of diabetic complications are there vealed changes in the bactericidal activity of segmented neutrophils. The trend of indicators of leukocyte formula and the distribution curve of mononuclear cells by size, as well as the growth of the lymphocyticgranulocytic index, indicate a chronic formation of endotoxin synthesize of diabetes. Conclusions. Lowering the level of cationic proteins, the activity of myeloperoxidase and the NBT-test under stimulation of neutrophil granulocytes bylectinsis a sign of unsatisfactory state of the bactericidal cells system, which may be the cause of chronic and acute inflammatory processes in the body that accompany type 2 diabetes, to a functional exhaustion of the macrophage link in the organism immune defense. Keywords: type 2 diabetes, purulent-inflammatory diseases of soft tissues, immunogenesis, cytomorphometry, cytogistochemistry, immunocompetent blood cells.

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001. ISOLATION AND CHARACTERISATION OF PORCINE ES CELLS

Reproduction Fertility and Development ◽

10.1071/srb09abs001 ◽

2009 ◽

Vol 21 (9) ◽

pp. 1

Author(s):

M. B. Nottle ◽

I. M. Vassiliev ◽

S. Vassilieva ◽

L. F. S. Beebe ◽

S. J. Harrison ◽

...

Keyword(s):

Inner Cell Mass ◽

Es Cells ◽

Cell Mass ◽

Embryonic Stem ◽

Cell Types ◽

Embryoid Bodies ◽

The Body ◽

Domestic Species ◽

Serum Replacement

Embryonic stem (ES) cellshave the capacity for self renewal, can remain undifferentiated in long term culture and can contribute to all the cells in the body including the germ cells. EScells have been isolated in mice and have also been described for humans. However despite considerable effort for more than two decades ES cellswhich can contribute to the germline are yet to be isolated for the pig or any domestic species for that matter. We have developed a new method for isolating porcine ES cells which uses whole embryos cultured in alpha MEM with 10% serum replacement plus additives under 5% O2. Unlike methods employed previously this method results in homogenous outgrowths whose cells resemble ES cells and which express Oct 4 and Nanog and SSEA-1 [1]. These cells can be passaged and cryopreserved repeatedly resulting in the establishment of cell lines at similar efficiencies to that reported previously for 129Sv mice [2]. These cells can form embryoid bodies and can be differentiated to various cell types representative of all three germ layers [3]. Following their injection into blastocysts these cells localise /become incorporated in the inner cell mass and can be used to produce chimaeras when these embryos are transferred to recipient animals [2]. To date we have produced chimaeric pigs from one male ES cell line [2]. These are currently being mated to demonstrate germline transmission. Future studies will examine the applicability of our method to other species commencing with mice and cattle before extending these to humans.

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Microparticles and acute lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00354.2011 ◽

2012 ◽

Vol 303 (5) ◽

pp. L364-L381 ◽

Cited By ~ 89

Author(s):

Mark McVey ◽

Arata Tabuchi ◽

Wolfgang M. Kuebler

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Blood Cells ◽

Immune Modulation ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Cell Types ◽

Severe Form ◽

Beneficial Effects ◽

Formation Function

The pathophysiology of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), is characterized by increased vascular and epithelial permeability, hypercoagulation and hypofibrinolysis, inflammation, and immune modulation. These detrimental changes are orchestrated by cross talk between a complex network of cells, mediators, and signaling pathways. A rapidly growing number of studies have reported the appearance of distinct populations of microparticles (MPs) in both the vascular and alveolar compartments in animal models of ALI/ARDS or respective patient populations, where they may serve as diagnostic and prognostic biomarkers. MPs are small cytosolic vesicles with an intact lipid bilayer that can be released by a variety of vascular, parenchymal, or blood cells and that contain membrane and cytosolic proteins, organelles, lipids, and RNA supplied from and characteristic for their respective parental cells. Owing to this endowment, MPs can effectively interact with other cell types via fusion, receptor-mediated interaction, uptake, or mediator release, thereby acting as intrinsic stimulators, modulators, or even attenuators in a variety of disease processes. This review summarizes current knowledge on the formation and potential functional role of different MPs in inflammatory diseases with a specific focus on ALI/ARDS. ALI has been associated with the formation of MPs from such diverse cellular origins as platelets, neutrophils, monocytes, lymphocytes, red blood cells, and endothelial and epithelial cells. Because of their considerable heterogeneity in terms of origin and functional properties, MPs may contribute via both harmful and beneficial effects to the characteristic pathological features of ALI/ARDS. A better understanding of the formation, function, and relevance of MPs may give rise to new promising therapeutic strategies to modulate coagulation, inflammation, endothelial function, and permeability either through removal or inhibition of “detrimental” MPs or through administration or stimulation of “favorable” MPs.

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