scholarly journals Glucosephosphate Isomerase Deficiency: Evidence for In Vivo Instability of an Enzyme Variant With Hemolysis

Blood ◽  
1973 ◽  
Vol 41 (5) ◽  
pp. 691-699 ◽  
Author(s):  
Heidwolf Arnold ◽  
Karl-Georg Blume ◽  
Rupert Engelhardt ◽  
Georg Wilhelm Löhr
Keyword(s):  
Blood Cells ◽  
Cell Populations ◽  
Red Cell ◽  
Glucosephosphate Isomerase ◽  
Metabolic Capacity ◽  
Comparable Amount ◽  
Glucose Phosphate ◽  
Enzyme Variant

Abstract Pathogenesis of hemolysis in glucose-phosphate isomerase (GPI) deficiency was studied. Red cell populations of different ages were obtained by density centrifugation. In comparison to cell populations with comparable amount of reticulocytes, GPI activity decreased faster in the deficient red cells. A method to simulate aging blood cells in vitro was devised. On the first day the rate of glycolysis was normal in the deficient cells, but by the eighth day of the incubation period, the metabolic capacity decreased markedly, and hemolysis was observed. Using mannose as a source of energy, the rate of glycolysis was still normal by the eighth day, which reflects the cause and effect relationship between impairment of energy metabolism and GPI deficiency. It may be concluded that hemolytic anemia in this case of GPI deficiency is caused by the synthesis of a qualitatively changed subunit of the GPI molecule, which is associated with faster inactivation of the enzyme in vivo.

scholarly journals 2,3-Diphosphoglycerate Content and Oxygen Affinity as a Function of Red Cell Age in Normal Individuals

Blood ◽  
1971 ◽  
Vol 38 (4) ◽  
pp. 463-467 ◽  
Author(s):  
STAVROS HAIDAS ◽  
DOMINIQUE LABIE ◽  
JEAN-CLAUDE KAPLAN
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Oxygen Affinity ◽  
Red Cell ◽  
In Vitro Storage ◽  
Cell Age ◽  
Normal Individuals ◽  
2,3 Dpg

Abstract A parallel decline of 2,3-diphosphoglycerate (2,3-DPG) and P50 of intracorpuscular hemoglobin is found in red blood cells during their in vivo aging. After 2,3-DPG depletion due to in vitro storage, the capacity to restore, 2,3-DPG in the presence of inosine is significantly impaired in senescent cells as compared with young cells.

scholarly journals Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo

2019 ◽  
Vol 3 (17) ◽  
pp. 2586-2597 ◽  
Author(s):  
Timothy J. McMahon ◽  
Siqing Shan ◽  
Daniel A. Riccio ◽  
Milena Batchvarova ◽  
Hongmei Zhu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Red Blood Cells ◽  
Ubiquitin Ligase ◽  
Blood Cells ◽  
Leukocyte Adhesion ◽  
Vascular Occlusion ◽  
Red Cell ◽  
Protein 4.1

Abstract Sickle red blood cells (SSRBCs) are adherent to the endothelium, activate leukocyte adhesion, and are deficient in bioactive nitric oxide (NO) adducts such as S-nitrosothiols (SNOs), with reduced ability to induce vasodilation in response to hypoxia. All these pathophysiologic characteristics promote vascular occlusion, the hallmark of sickle cell disease (SCD). Loading hypoxic SSRBCs in vitro with NO followed by reoxygenation significantly decreased epinephrine-activated SSRBC adhesion to the endothelium, the ability of activated SSRBCs to mediate leukocyte adhesion in vitro, and vessel obstruction in vivo. Because transfusion is frequently used in SCD, we also determined the effects of banked (SNO-depleted) red blood cells (RBCs) on vaso-occlusion in vivo. Fresh or 14-day-old normal RBCs (AARBCs) reduced epinephrine-activated SSRBC adhesion to the vascular endothelium and prevented vaso-occlusion. In contrast, AARBCs stored for 30 days failed to decrease activated SSRBC adhesivity or vaso-occlusion, unless these RBCs were loaded with NO. Furthermore, NO loading of SSRBCs increased S-nitrosohemoglobin and modulated epinephrine’s effect by upregulating phosphorylation of membrane proteins, including pyruvate kinase, E3 ubiquitin ligase, and the cytoskeletal protein 4.1. Thus, abnormal SSRBC NO/SNO content both contributes to the vaso-occlusive pathophysiology of SCD, potentially by affecting at least protein phosphorylation, and is potentially amenable to correction by (S)NO repletion or by RBC transfusion.

VERY LARGE AND COMPACT AGGREGATES OF RED CELLS IN HEART DISEASE AND CANCER: POSSIBLY AN ANALOGOUS ROLE IN THE MICROCIRCULATION AS PLATELET AGGREGATES

1987 ◽  
Author(s):  
L Dintenfass
Keyword(s):  
Blood Cells ◽  
Red Cells ◽  
Cell Aggregates ◽  
Red Cell ◽  
Compact Type ◽  
Platelet Aggregates ◽  
The One ◽  
Native Plasma

Very large aggregates of red blood cells, showing compact morphology, are easily observed in vitro, and might be of importance in the in vivo microcirculation. Blood from patients with myocardial infarction, WaldenstrBm1s macroglobulinaemia, or varoous carcinomas. etc., was anticoagulated with EDTA, and adjusted to haematocrit of 0.30, using native plasma. All tests were carried out in the slit-capillary photoviscometer, at temp, of 22°C. Micro and macrophotographs were taken during flow and stasis, using slits of 12.5 and 50 micron gaps. Studies showed that very large (two-dimensional) red cell aggregates are formed, such aggregates (clumps) containing up to 50,000 red cells in a single clump. The architecture of such aggregates differed according to the origin of blood: both rouleaux type and random / compact type of aggregates were observed; in principle, a spectrum of morphologies can be seen. These observations form a link between the earlier work of FAHRAEUS, on the one hand, and that of KNISELY, on the other; whic works appeared at the time to be contradictory and irreconcilable.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

LACK OF EFFECT OF CORTICOSTEROIDS ON THE IN VIVO DISAPPEARANCE OF SULFHYDRYL-INHIBITED AND ANTIBODY-COATED ERYTHROCYTES

1964 ◽  
Vol 47 (3_Suppl) ◽  
pp. S28-S36
Author(s):  
Kailash N. Agarwal
Keyword(s):  
Red Cells ◽  
List Type ◽  
Red Cell

ABSTRACT Red cells were incubated in vitro with sulfhydryl inhibitors and Rhantibody with and without prior incubation with prednisolone-hemisuccinate. These erythrocytes were labelled with Cr51 and P32 and their disappearance in vivo after autotransfusion was measured. Prior incubation with prednisolone-hemisuccinate had no effect on the rate of red cell disappearance. The disappearance of the cells was shown to take place without appreciable intravascular destruction.

Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 305-319 ◽  
Author(s):  
Marietta Herrmann ◽  
Franz Jakob
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Cell Populations ◽  
Surface Markers ◽  
Bone Marrow Niches

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem cells possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has been suggested to define MSCs in vitro, including adhesion to plastic, expression of typical surface markers and the ability to differentiate towards the adipogenic, osteogenic and chondrogenic lineages but they are critically discussed since the differentiation capability of cells could not always be confirmed by stringent assays in vivo. However, these in vitro characteristics have led to the notion that progenitor cell populations, similar to MSCs in bone marrow, reside in various tissues. MSCs are in the focus of numerous (pre)clinical studies on tissue regeneration and repair.Recent advances in terms of genetic animal models enabled a couple of studies targeting skeletal progenitor cells in vivo. Accordingly, different skeletal progenitor cell populations could be identified by the expression of surface markers including nestin and leptin receptor. While there are still issues with the identity of, and the overlap between different cell populations, these studies suggested that specific microenvironments, referred to as niches, host and maintain skeletal progenitor cells in the bone marrow. Dynamic mutual interactions through biological and physical cues between niche constituting cells and niche inhabitants control dormancy, symmetric and asymmetric cell division and lineage commitment. Niche constituting cells, inhabitant cells and their extracellular matrix are subject to influences of aging and disease e.g. via cellular modulators. Protective niches can be hijacked and abused by metastasizing tumor cells, and may even be adapted via mutual education. Here, we summarize the current knowledge on bone marrow skeletal progenitor cell niches in physiology and pathophysiology. We discuss the plasticity and dynamics of bone marrow niches as well as future perspectives of targeting niches for therapeutic strategies.

scholarly journals Multimodal Diagnostics of Microrheologic Alterations in Blood of Coronary Heart Disease and Diabetic Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 76
Author(s):  
Anastasia Maslianitsyna ◽  
Petr Ermolinskiy ◽  
Andrei Lugovtsov ◽  
Alexandra Pigurenko ◽  
Maria Sasonko ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Optical Methods ◽  
Diabetic Patients ◽  
Aggregation Index ◽  
Significant Difference

Coronary heart disease (CHD) has serious implications for human health and needs to be diagnosed as early as possible. In this article in vivo and in vitro optical methods are used to study blood properties related to the aggregation of red blood cells in patients with CHD and comorbidities such as type 2 diabetes mellitus (T2DM). The results show not only a significant difference of the aggregation in patients compared to healthy people, but also a correspondence between in vivo and in vitro parameters. Red blood cells aggregate in CHD patients faster and more numerously; in particular the aggregation index increases by 20 ± 7%. The presence of T2DM also significantly elevates aggregation in CHD patients. This work demonstrates multimodal diagnostics and monitoring of patients with socially significant pathologies.

scholarly journals PMN-MDSCs Enhance CTC Metastatic Properties through Reciprocal Interactions via ROS/Notch/Nodal Signaling

2019 ◽  
Vol 20 (8) ◽  
pp. 1916 ◽  
Author(s):  
Marc L. Sprouse ◽  
Thomas Welte ◽  
Debasish Boral ◽  
Haowen N. Liu ◽  
Wei Yin ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Receptor Expression ◽  
Cell Populations ◽  
Nodal Signaling ◽  
Breast Cancer Patients ◽  
Tumoricidal Activity ◽  
Notch Activation ◽  
Notch1 Receptor

Intratumoral infiltration of myeloid-derived suppressor cells (MDSCs) is known to promote neoplastic growth by inhibiting the tumoricidal activity of T cells. However, direct interactions between patient-derived MDSCs and circulating tumors cells (CTCs) within the microenvironment of blood remain unexplored. Dissecting interplays between CTCs and circulatory MDSCs by heterotypic CTC/MDSC clustering is critical as a key mechanism to promote CTC survival and sustain the metastatic process. We characterized CTCs and polymorphonuclear-MDSCs (PMN-MDSCs) isolated in parallel from peripheral blood of metastatic melanoma and breast cancer patients by multi-parametric flow cytometry. Transplantation of both cell populations in the systemic circulation of mice revealed significantly enhanced dissemination and metastasis in mice co-injected with CTCs and PMN-MDSCs compared to mice injected with CTCs or MDSCs alone. Notably, CTC/PMN-MDSC clusters were detected in vitro and in vivo either in patients’ blood or by longitudinal monitoring of blood from animals. This was coupled with in vitro co-culturing of cell populations, demonstrating that CTCs formed physical clusters with PMN-MDSCs; and induced their pro-tumorigenic differentiation through paracrine Nodal signaling, augmenting the production of reactive oxygen species (ROS) by PMN-MDSCs. These findings were validated by detecting significantly higher Nodal and ROS levels in blood of cancer patients in the presence of naïve, heterotypic CTC/PMN-MDSC clusters. Augmented PMN-MDSC ROS upregulated Notch1 receptor expression in CTCs through the ROS-NRF2-ARE axis, thus priming CTCs to respond to ligand-mediated (Jagged1) Notch activation. Jagged1-expressing PMN-MDSCs contributed to enhanced Notch activation in CTCs by engagement of Notch1 receptor. The reciprocity of CTC/PMN-MDSC bi-directional paracrine interactions and signaling was functionally validated in inhibitor-based analyses, demonstrating that combined Nodal and ROS inhibition abrogated CTC/PMN-MDSC interactions and led to a reduction of CTC survival and proliferation. This study provides seminal evidence showing that PMN-MDSCs, additive to their immuno-suppressive roles, directly interact with CTCs and promote their dissemination and metastatic potency. Targeting CTC/PMN-MDSC heterotypic clusters and associated crosstalks can therefore represent a novel therapeutic avenue for limiting hematogenous spread of metastatic disease.

scholarly journals Inhibition of platelet phagocytosis as an in vitro predictor for therapeutic potential of RBC antibodies in murine ITP

Blood ◽  
2020 ◽  
Vol 135 (26) ◽  
pp. 2420-2424 ◽  
Author(s):  
Ramsha Khan ◽  
Melissa Menard ◽  
Chao-Ching Jen ◽  
Xi Chen ◽  
Peter A. A. Norris ◽  
...  
Keyword(s):  
Blood Cells ◽  
Immune Thrombocytopenia ◽  
Therapeutic Potential ◽  
Sufficient Condition ◽  
First Line ◽  
Phagocytosis Assay ◽  
First Line Therapy ◽  
Line Therapy

Abstract Polyclonal anti-D is a first-line therapy for immune thrombocytopenia (ITP). Monoclonal antibodies are desirable alternatives, but none have yet proven successful despite their ability to opsonize erythrocytes (or red blood cells, RBCs) and cause anemia. Here, we examined 12 murine erythrocyte–specific antibodies of different specificity and subtypes and found that 8 of these antibodies could induce anemia in antigen-positive mice. Of these 8 antibodies, only 5 ameliorated ITP. All antibodies were examined for their in vitro ability to support macrophage-mediated phagocytosis of erythrocytes. Antibodies which supported erythrocyte phagocytosis in vitro successfully ameliorated ITP in vivo. To examine the ability of each antibody to inhibit phagocytosis of platelets, the antibodies were used to sensitize erythrocytes in vitro and these were added to a platelet phagocytosis assay. Antibodies that inhibited platelet phagocytosis in vitro also all ameliorated ITP in vivo. We conclude that inducing anemia is not a sufficient condition for amelioration of ITP but that the antibody’s ability to prevent platelet phagocytosis in vitro predicted its ability to ameliorate ITP. We suggest that inhibition of in vitro platelet phagocytosis may prove to be a valuable tool for determining which erythrocyte antibodies would likely be candidates for clinical use in ITP.

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