scholarly journals On Demand Recruitment of Macrophages Is Required for Erythroid Niche Formation during Stress Erythropoiesis in the Bone Marrow

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 848-848
Author(s):  
Verena Petzer ◽  
Piotr Tymoszuk ◽  
Felix Böhm ◽  
Markus Seifert ◽  
Sieghart Sopper ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Iron Availability ◽  
Stress Erythropoiesis ◽  
Iron Supply ◽  
Reporter Mice

Abstract Every second more than 2 million new erythrocytes are released from the bone marrow of human adults, highlighting the tremendous turn-over of these cells. In parallel to hematopoietic stem cell niches, the last stages of erythropoiesis take place in specialized bone marrow niches, termed 'erythroid niches'. Concretely, the erythroid niche is composed of a 'central macrophage' which is surrounded by erythroid progenitor cells. Regardless of steady-state or stress erythropoiesis, iron availability is, beside erythropoietin, a key factor determining erythroid output and red blood cell quality, as reflected by hemoglobin content of these cells. It is well established that systemic iron availability for erythropoiesis, in the form of iron saturated transferrin (Tf), is mainly maintained via a recycling process of senescent red blood cells, which takes place in macrophages of the reticuloendothelial system. Yet, it is still a matter of debate if also central macrophages are involved in iron supply for red blood cell development in a more direct way due to their close proximity to developing red blood cells. Using a myeloid-specific knockout mouse strain, lacking the solely known iron exporter ferroportin (Fpn; Fpnfl/flLysMCre+/+ mice) and specific reporter mice (ROSA26tdTomatofl/fl Cx3cr1CreERT2 mice), we examined the connection between iron metabolism, erythropoiesis and central macrophages. Analysis of Fpnfl/flLysMCre+/+ animals at steady state revealed microcytic anemia, higher tissue iron loading, reduced hepatic hepcidin expression and distorted erythroid precursor population distribution in the bone marrow with no significant chances in Tf saturation (Tf-Sat). The latter is giving a first hint, that local bone marrow Fpn expression on macrophages may be important for iron supply for erythropoiesis. Strikingly, further work up via flow cytometry demonstrated that disturbances seen in bone marrow erythropoiesis were accompanied by nearby loss of resident bone marrow macrophages (defined as CD11blo, F4/80pos, MerTKpos). In parallel, a CD11bhi, F4/80pos, MerTKpos population came into existence, suggesting that these cells may compensate for the loss of 'canonical' central macrophages. Attempting to explain these intriguing results, we sought to investigate differentiation pathways and turnover of bone marrow central macrophages. First, we used the ROSA26tdTomatofl/fl Cx3cr1CreERT2 monocyte-specific reporter mice and techniques of transient monocyte labelling in utero and in adult phlebotomized animals to determine the origin of central macrophages. We could show that those cells undergo constant replenishment by circulating monocytes. Notably, the rate of this process got markedly increased upon recovery from blood loss and concomitant expansion of the central macrophage population. Second, by administration of a CCR2/CCR5 inhibitor (cenicriviroc), diminishing monocyte egress from the bone marrow and tissue infiltration, we could demonstrate decreased reticulocyte count during stress erythropoiesis, thus strengthening the direct impact of macrophages to support effective erythroid output. Next, effects of stress-induced erythropoiesis were investigated in Fpnfl/flLysMCre+/+ compared to Fpnfl/flLysMCre-/- mice. Amelioration of anemia after phlebotomy was extended, microcytosis was more pronounced and reticulocyte egress was diminished but prolonged. Of interest, Fpnfl/flLysMCre+/+ mice on a diet containing an 8-times higher iron content during phlebotomy, thus transiently increasing Tf-Sat, recovered from anemia wildtype-like. These results indicate that stress erythropoiesis with a high iron demand depends, under normal iron availability, in part on central macrophages and their nursing function to overcome the increased demand of iron. Ongoing experiments aim to identify how recruited bone marrow macrophages, i.e. central macrophages, contribute to erythropoiesis during stress - if central macrophages directly supply developing erythroid cells with iron in a Tf-free fashion or, if they are suppliers of additional growth factors that work synergistically with the Tf-bound iron to drive hemoglobin production. In summary our data clearly show that macrophages need to be recruited to the bone marrow for effective erythroid output during stress erythropoiesis. Disclosures Weiss: Kymab Ltd.: Consultancy. Theurl:Kymab Ltd.: Consultancy, Research Funding.

scholarly journals A theoretical investigation of the frisbee motion of red blood cells in shear flow

2021 ◽  
Vol 16 ◽  
pp. 23
Author(s):  
Thierry Mignon ◽  
Simon Mendez
Keyword(s):  
Steady State ◽  
Shear Flow ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Numerical Solutions ◽  
Shear Rates ◽  
Steady State Solutions ◽  
Low Shear

The dynamics of a single red blood cell in shear flow is a fluid–structure interaction problem that yields a tremendous richness of behaviors, as a function of the parameters of the problem. A low shear rates, the deformations of the red blood cell remain small and low-order models have been developed, predicting the orientation of the cell and the membrane circulation along time. They reproduce the dynamics observed in experiments and in simulations, but they do not simplify the problem enough to enable simple interpretations of the phenomena. In a process of exploring the red blood cell dynamics at low shear rates, an existing model constituted of 5 nonlinear ordinary differential equations is rewritten using quaternions to parametrize the rotations of the red blood cell. Techniques from algebraic geometry are then used to determine the steady-state solutions of the problems. These solutions are relevant to a particular regime where the red blood cell reaches a constant inclination angle, with its membrane rotating around it, and referred to as frisbee motion. Comparing the numerical solutions of the model to the steady-state solutions allows a better understanding of the transition between the most emblematic motions of red blood cells, flipping and tank-treading.

CLINICAL STUDIES OF THE EFFECTS OF 3,5,5, TRIMETHYLOXAZOLIDINE-2-4-DIONE (TRIDIONE®) ON THE HEMATOPOIETIC SYSTEM, LIVER AND KIDNEY

PEDIATRICS ◽  
1950 ◽  
Vol 5 (4) ◽  
pp. 695-707
Author(s):  
ERIC DENHOFF ◽  
MAURICE W. LAUFER
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Blood Platelet ◽  
Clot Retraction ◽  
Nucleated Red Blood Cells ◽  
Complete Blood Counts ◽  
Nucleated Red Blood Cell

Six children receiving tridione® showed : 1. A constant syndrome of : a decline in bone marrow megakaryocyte and nucleated red blood cell elements; a low peripheral blood platelet count; and prolonged clot retraction time. 2. An occasional association of: peripheral leukopenia, toxic signs in the red blood cells and lymphocytes, and an abnormal cephalin flocculation response. In one case the bone marrow megakaryocyte response occurred alone and was temporary; in another it was temporary but associated with a persistent decline in marrow nucleated red blood cells; and in a third case both the megakaryocyte and nucleated red blood cell depression were only temporary, despite continuation of the medication. Withdrawal of medication caused a return to normal values, most rapid and marked in the bone marrow. Tests for clot retraction time and platelet counts at regular intervals in addition to complete blood counts seem indicated in all patients receiving tridione®. When available, bone marrow studies, especially of megakaryocytes, would also be of value.

Microfluidic electrical impedance assessment of red blood cell mediated microvascular occlusion

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Yuncheng Man ◽  
Debnath Maji ◽  
Ran An ◽  
Sanjay Ahuja ◽  
Jane A Little ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Electrical Impedance ◽  
Cell Disease ◽  
Blood Disorders

Alterations in the deformability of red blood cells (RBCs), occurring in hemolytic blood disorders such as sickle cell disease (SCD), contributes to vaso-occlusion and disease pathophysiology. However, there are few...

Permeation of the luminal capillary glycocalyx is determined by hyaluronan

1999 ◽  
Vol 277 (2) ◽  
pp. H508-H514 ◽  
Author(s):  
Charmaine B. S. Henry ◽  
Brian R. Duling
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Enzyme Treatment ◽  
Apical Surface ◽  
Bright Field ◽  
Endothelial Surface ◽  
The Difference

The endothelial cell glycocalyx influences blood flow and presents a selective barrier to movement of macromolecules from plasma to the endothelial surface. In the hamster cremaster microcirculation, FITC-labeled Dextran 70 and larger molecules are excluded from a region extending almost 0.5 μm from the endothelial surface into the lumen. Red blood cells under normal flow conditions are excluded from a region extending even farther into the lumen. Examination of cultured endothelial cells has shown that the glycocalyx contains hyaluronan, a glycosaminoglycan which is known to create matrices with molecular sieving properties. To test the hypothesis that hyaluronan might be involved in establishing the permeation properties of the apical surface glycocalyx in vivo, hamster microvessels in the cremaster muscle were visualized using video microscopy. After infusion of one of several FITC-dextrans (70, 145, 580, and 2,000 kDa) via a femoral cannula, microvessels were observed with bright-field and fluorescence microscopy to obtain estimates of the anatomic diameters and the widths of fluorescent dextran columns and of red blood cell columns (means ± SE). The widths of the red blood cell and dextran exclusion zones were calculated as one-half the difference between the bright-field anatomic diameter and the width of the red blood cell column or dextran column. After 1 h of treatment with active Streptomyces hyaluronidase, there was a significant increase in access of 70- and 145-kDa FITC-dextrans to the space bounded by the apical glycocalyx, but no increase in access of the red blood cells or in the anatomic diameter in capillaries, arterioles, and venules. Hyaluronidase had no effect on access of FITC-Dextrans 580 and 2,000. Infusion of a mixture of hyaluronan and chondroitin sulfate after enzyme treatment reconstituted the glycocalyx, although treatment with either molecule separately had no effect. These results suggest that cell surface hyaluronan plays a role in regulating or establishing permeation of the apical glycocalyx to macromolecules. This finding and our prior observations suggest that hyaluronan and other glycoconjugates are required for assembly of the matrix on the endothelial surface. We hypothesize that hyaluronidase creates a more open matrix, enabling smaller dextran molecules to penetrate deeper into the glycocalyx.

Susceptibility of density-fractionated erythrocytes to subhaemolytic mechanical shear stress

2018 ◽  
Vol 42 (3) ◽  
pp. 151-157 ◽  
Author(s):  
Antony P McNamee ◽  
Kieran Richardson ◽  
Jarod Horobin ◽  
Lennart Kuck ◽  
Michael J Simmonds
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Shear Stresses ◽  
Mechanical Stimuli ◽  
Cell Deformability ◽  
Red Blood Cell Deformability ◽  
Cell Age ◽  
Low Shear

Introduction: Accumulating evidence demonstrates that subhaemolytic mechanical stresses, typical of circulatory support, induce physical and biochemical changes to red blood cells. It remains unclear, however, whether cell age affects susceptibility to these mechanical forces. This study thus examined the sensitivity of density-fractionated red blood cells to sublethal mechanical stresses. Methods: Red blood cells were isolated and washed twice, with the least and most dense fractions being obtained following centrifugation (1500 g × 5 min). Red blood cell deformability was determined across an osmotic gradient and a range of shear stresses (0.3–50 Pa). Cell deformability was also quantified before and after 300 s exposure to shear stresses known to decrease (64 Pa) or increase (10 Pa) red blood cell deformability. The time course of accumulated sublethal damage that occurred during exposure to 64 Pa was also examined. Results: Dense red blood cells exhibited decreased capacity to deform when compared with less dense cells. Cellular response to mechanical stimuli was similar in trend for all red blood cells, independent of density; however, the magnitude of impairment in cell deformability was exacerbated in dense cells. Moreover, the rate of impairment in cellular deformability, induced by 64 Pa, was more rapid for dense cells. Relative improvement in red blood cell deformability, due to low-shear conditioning (10 Pa), was consistent for both cell populations. Conclusion: Red blood cell populations respond differently to mechanical stimuli: older (more dense) cells are highly susceptible to sublethal mechanical trauma, while cell age (density) does not appear to alter the magnitude of improved cell deformability following low-shear conditioning.

scholarly journals Small Red Blood Cell Fraction on the UF-1000i Urine Analyzer as a Screening Tool to Detect Dysmorphic Red Blood Cells for Diagnosing Glomerulonephritis

2019 ◽  
Vol 39 (3) ◽  
pp. 271
Author(s):  
Hyunjung Kim ◽  
Young Ok Kim ◽  
Yonggoo Kim ◽  
Jin-Soon Suh ◽  
Eun-Jung Cho ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Screening Tool ◽  
Cell Fraction

scholarly journals PO-283 Correlation Analysis between Blood Cell Viability, Five Elements and Competition Performance of Elite Men’s Rowers

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Junbei Bai
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Aerobic Capacity ◽  
Red Blood Cell ◽  
Iron Content ◽  
Blood Cells ◽  
White Blood Cells ◽  
Cell Activity ◽  
Ordinary People ◽  
Five Elements

Objective To observe the national elite male rowers blood, red blood cell activity and serum copper, zinc, calcium, magnesium and iron content of the five elements, and compared with the ordinary people. Aimed to investigate the between athletes, athletes and ordinary differences between the two sets of indicators and to explore the impact of element contents in red blood cell activity and five factors. Trying to bring two sets of indicators and specific combining ability, used in training on the monitoring function, and for the future to provide some references for further study. Methods It was included 22 athletes and 22 ordinary men, as the research object, in the collection of blood, measuring red blood cell activity in the blood content of the five elements, simultaneous measurement of physical indicators , will be doing all the data at the differences between the two groups compared to the group to do correlation analysis. The recent record of 2000m, 6000m rowing Dynamometer test results, and red blood cell activity associated with the five elements of content analysis. Results 1. Athletes indicators related to aerobic exercise were significantly higher than ordinary people. The white blood cells of athletes group were average.It shows that athletes have high aerobic capacity, while white blood cells are more stable than normal people. The members of the national rowing men's iron, magnesium content was significantly higher than ordinary group, the iron content is higher than the normal reference value; blood calcium levels were significantly lower than ordinary people, and lower than the normal reference value. The total number of red blood cells and the number of living cells was very significant positive correlation in two groups subjects; Red blood cell activity and red blood cell diameter is proportional, and red blood cell roundness in inverse proportion to the relationship; from this experiment a special ability to see red blood cell activity and there is no correlation. In both groups, hemoglobin was positively correlated with iron content, while iron was positively correlated with copper content. Conclusions 1. Increasing the number and volume of red blood cells can effectively increase the activity of red blood cells; red blood cell activity has no correlation with specific ability, and can not be used as an indicator to determine specific ability. The content of iron and magnesium in rowers is higher than that in ordinary people, which indicates that the adjustment of aerobic capacity and nerve control is very effective. The lower calcium content indicates that the injury caused by calcium loss should be prevented and the urgency of calcium supplementation should be emphasized. In training, we should pay attention to increasing hemoglobin content and aerobic capacity by supplementing iron. We can further consider the effect of supplementing copper to promote iron supplementation.

scholarly journals Accounting for red blood cell accessibility reveals distinct invasion strategies inPlasmodium falciparumstrains

2019 ◽  
Author(s):  
Francisco Cai ◽  
Tiffany M. DeSimone ◽  
Elsa Hansen ◽  
Cameron V. Jennings ◽  
Amy K. Bei ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Cell Structure ◽  
Clinical Manifestations ◽  
Parasite Growth ◽  
Invasion Pathways ◽  
Invasion Rate

AbstractThe growth of the malaria parasitePlasmodium falciparumin human blood causes all clinical manifestations of malaria, a process that begins with the invasion of red blood cells. Parasites enter red blood cells using distinct pairs of parasite ligands and host receptors that define particular invasion pathways. Parasite strains have the capacity to switch between invasion pathways. This flexibility is thought to facilitate immune evasion against particular parasite ligands, but may also reflect the fact that red blood cell surfaces are dynamic and composed of heterogeneous invasion targets. Different host genetic backgrounds affecting red blood cell structure have long been recognized to impact parasite growthin vivo, but even within a host, red blood cells undergo dramatic changes in morphology and receptor density as they age. The consequences of these heterogeneities for parasite growthin vivoremain unclear. Here, we measured the ability of laboratory strains ofP. falciparumrelying on distinct invasion pathways to enter red blood cells of different ages. We estimated invasion efficiency while accounting for the fact that even if the red blood cells display the appropriate receptors, not all are physically accessible to invading parasites. This approach revealed a tradeoff made by parasites between the fraction of susceptible cells and their invasion rate into them. We were able to distinguish between “specialist” strains exhibiting high invasion rate in fewer cells versus “generalist” strains invading less efficiently into a larger fraction of cells. We developed a mathematical model to predict that infection with a generalist strain would lead to higher peak parasitemiasin vivowhen compared with a specialist strain with similar overall proliferation rate. Thus, the heterogeneous ecology of red blood cells may play a key role in determining the rate of parasite proliferation between different strains ofP. falciparum.

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