scholarly journals Absence of the Adaptor Protein PEA-15 Is Associated with Altered Pattern of Th Cytokines Production by Activated CD4+ T Lymphocytes In Vitro, and Defective Red Blood Cell Alloimmune Response In Vivo

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0136885 ◽  
Author(s):  
Stéphane Kerbrat ◽  
Benoit Vingert ◽  
Marie-Pierre Junier ◽  
Flavia Castellano ◽  
François Renault-Mihara ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Adaptor Protein

ASPIRIN MODIFIES RED BLOOD CELL BEHAVIOUR (RBC) IN THE PLATELET-RBC INTERACTION

1987 ◽  
Author(s):  
M T Santos ◽  
J Aznar ◽  
J Valles ◽  
J L Perez-Reguejo
Keyword(s):  
Single Dose ◽  
Blood Cell ◽  
Platelet Activation ◽  
Red Blood Cell ◽  
Normal Subjects ◽  
Antithrombotic Agent ◽  
Cell Behaviour ◽  
Insight Into

RBC stimulate the initial stages of platelet activation by collagen as evaluated by the BASIC wave (Perez-Requejo et al. Thromb Haemostas 54:799 1985). In order to get some insight into the mechanisms of platelet-RBC interactions, a BASIC wave was induced by lug/ml of collagen after mixing "in vitro" platelets and RBC obtained both before and two hours after a single dose of 500 mg of ASA from normal subjects. The TXB2 formed was also evaluated. The results show (Table) that non aspirinized RBC (non-ASA-RBC) increase the BASIC wave intensity of aspirinized platelets (ASA-PRP) by a cyclooxygenase-independent pathway since no increase in TXB2 was observed (Exp 1), while both non-ASA-RBC (Exp 2) and ASA-RBC (Exp 3) activate non-ASA platelets with theparticipation of the cyclooxygenase system, since an increase in TXA2 was found.A comparison of the effect of non-ASA-RBC (Exp 1) and ASA-RBC (Exp 4) on aspirinized platelets shows that ASA modifies the RBC behaviour associated with estimulation of platelets by a cyclooxygenase-independent pathway. This effect of ASA on RBC is nottransient and lasts at least 48 hours after ASA ingestion. In addition, when asmall proportion of nonASA platelets (10%) is mixed with aspirinized platelets(90%) and ASA-RBC - a situation that can be encountered "in vivo" inthe hours following ASA ingestion - the intensity of the BASIC wave is 89% of that obtained when all the platelets are non aspirinized. This RBC effect on the mixtureof ASA and nonASA platelets, may help explain the sometimes contradictory effect of ASA as an antithrombotic agent.

The Presence of Novel Amino Acids in the Cytoplasmic Domain of Stem Cell Factor Results in Hematopoietic Defects inSteel17H Mice

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 1915-1925 ◽  
Author(s):  
Reuben Kapur ◽  
Ryan Cooper ◽  
Xingli Xiao ◽  
Mitchell J. Weiss ◽  
Peter Donovan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Bone Marrow ◽  
Biological Activity ◽  
Stem Cell ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Stem Cell Factor ◽  
Cytoplasmic Domain

Abstract Stem cell factor (SCF) is expressed as an integral membrane growth factor that may be differentially processed to produce predominantly soluble (S) (SCF248) or membrane-associated (MA) (SCF220) protein. A critical role for membrane presentation of SCF in the hematopoietic microenvironment (HM) has been suggested from the phenotype of the Steel-dickie(Sld) mice, which lack MA SCF, and by studies performed in our laboratory (and by others) using long-term bone marrow cultures and transgenic mice expressing different SCF isoforms.Steel17H (Sl17H) is an SCF mutant that demonstrates melanocyte defects and sterility in males but not in females. The Sl17H allele contains a intronic mutation resulting in the substitution of 36 amino acids (aa’s) in the SCF cytoplasmic domain with 28 novel aa’s. This mutation, which affects virtually the entire cytoplasmic domain of SCF, could be expected to alter membrane SCF presentation. To investigate this possibility, we examined the biochemical and biologic properties of the Sl17H-encoded protein and its impact in vivo and in vitro on hematopoiesis and on c-Kit signaling. We demonstrate that compound heterozygous Sl/Sl17H mice manifest multiple hematopoietic abnormalities in vivo, including red blood cell deficiency, bone marrow hypoplasia, and defective thymopoiesis. In vitro, both S and MA Sl17H isoforms of SCF exhibit reduced cell surface expression on stromal cells and diminished biological activity in comparison to wild-type (wt) SCF isoforms. These alterations in presentation and biological activity are associated with a significant reduction in the proliferation of an SCF-responsive erythroid progenitor cell line and in the activation of phosphatidylinositol 3-Kinase/Akt and mitogen-activated protein-Kinase signaling pathways. In vivo, transgene expression of the membrane-restricted (MR) (SCFX9/D3) SCF in Sl/Sl17H mutants results in a significant improvement in peripheral red blood cell counts in comparison toSl/Sl17H mice.

Pathophysiology of Thrombocytopenia and Anemia in Mice Lacking Transcription Factor NF-E2

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3037-3047 ◽  
Author(s):  
Jack Levin ◽  
Jin-Peng Peng ◽  
Georgiann R. Baker ◽  
Jean-Luc Villeval ◽  
Patrick Lecine ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Fetal Life ◽  
Wild Type ◽  
Cell Lineages ◽  
Cell Fragments ◽  
Proliferation Potential

Abstract Expression of the p45 subunit of transcription factor NF-E2 is restricted to selected blood cell lineages, including megakaryocytes and developing erythrocytes. Mice lacking p45 NF-E2 show profound thrombocytopenia, resulting from a late arrest in megakaryocyte differentiation, and a number of red blood cell defects, including anisocytosis and hypochromia. Here we report results of studies aimed to explore the pathophysiology of these abnormalities. Mice lacking NF-E2 produce very few platelet-like particles that display highly disorganized ultrastructure and respond poorly to platelet agonists, features consistent with the usually lethal hemorrhage in these animals. Thrombocytopenia was evident during fetal life and was not corrected by splenectomy in adults. Surprisingly, fetal NF-E2–deficient megakaryocyte progenitors showed reduced proliferation potential in vitro. Thus, NF-E2 is required for regulated megakaryocyte growth as well as for differentiation into platelets. All the erythroid abnormalities were reproduced in lethally irradiated wild-type recipients of hematopoietic cells derived from NF-E2-null fetuses. Whole blood from mice lacking p45 NF-E2 showed numerous small red blood cell fragments; however, survival of intact erythrocytes in vivo was indistinguishable from control mice. Considered together, these observations indicate a requirement for NF-E2 in generating normal erythrocytes. Despite impressive splenomegaly at baseline, mice lacking p45 NF-E2 survived splenectomy, which resulted in increased reticulocyte numbers. This reveals considerable erythroid reserve within extra-splenic sites of hematopoiesis and suggests a role for the spleen in clearing abnormal erythrocytes. Our findings address distinct aspects of the requirements for NF-E2 in blood cell homeostasis and establish its roles in proper differentiation of megakaryocytes and erythrocytes.

Abnormal Erythropoiesis in Microgravity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3701-3701 ◽  
Author(s):  
Kun Xu ◽  
Keith V. Holubec ◽  
John E. Love ◽  
Thomas J. Goodwin ◽  
Arthur J. Sytkowski
Keyword(s):  
Blood Cell ◽  
Cell Line ◽  
Red Blood Cell ◽  
Bone Marrow Cells ◽  
Cell Mass ◽  
Erythroid Cell ◽  
Specific Marker ◽  
Murine Erythroleukemia

Abstract Humans and experimental animals subjected to microgravity, such as experienced during space flight, exhibit alterations in erythropoiesis, including changes in red blood cell morphology, survival and a reduction in red blood cell mass. Some of these alterations have been attributed to a disruption of normal in vivo erythropoietin physiology. However, human bone marrow cells grown on orbit showed a profound reduction in the number of erythroid cells, suggesting a cellular component. We now report the results of a study carried out on orbit on the International Space Station (ISS UF-1) in which an erythroid cell line was induced to differentiate. Rauscher murine erythroleukemia cells, a continuous cell line that can undergo erythropoietin (Epo)- or chemical-induced differentiation similar to normal erythropoiesis, were cultured for 6 days either in microgravity on board the ISS or on earth and then for 3 days in the absence or presence of 50 U Epo/ml or 0.7% dimethyl sulfoxide (DMSO). The cells were fixed, stored on orbit and returned to earth for study. Compared to ground-based controls, cells cultured in microgravity exhibited a greater degree of differentiation (hemoglobinization) (p<0.01). However, TER-119 antigen, a specific marker of the late stages of murine erythroid differentiation, was not detected on the surface of cells grown in microgravity. A significantly higher percentage (p<0.05) of cell clusters formed on orbit, whereas actin content appeared reduced. Furthermore, there was a more profound loss of actin stress fibers in microgravity following Epo or DMSO treatment. These results demonstrate abnormal erythropoiesis in vitro in microgravity and are consistent with the hypothesis that erythropoiesis is affected by gravitational forces at the cellular level.(Supported by NASA Grants NAG9-1368 and NAG2-1592 to AJS)

scholarly journals Retrovirus-induced feline pure red blood cell aplasia: pathogenesis and response to suramin

Blood ◽  
1991 ◽  
Vol 77 (7) ◽  
pp. 1442-1451
Author(s):  
JL Abkowitz
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Transcriptase Inhibitor ◽  
Feline Leukemia Virus ◽  
Erythroid Progenitors ◽  
Marrow Cultures

Feline leukemia virus, subgroup C/Sarma (FeLV-C/Sarma) induces pure red blood cell aplasia in cats. Although erythroid (BFU-E and CFU-E) and granulocyte/macrophage (CFU-GM) progenitors are infected with this virus, only erythropoiesis is impaired. Two to 3 weeks before the onset of anemia, CFU-E become undetectable in marrow cultures while earlier erythroid progenitors (BFU-E) persist, suggesting that FeLV-C/Sarma (presumably via its envelope glycoprotein gp70) inhibits the differentiation of BFU-E to CFU-E in vivo. To correlate in vitro observations with the progression of disease, prospective studies were performed in six cats. These studies showed that at the time that the frequencies of CFU-E decreased in marrow cultures, BFU-E no longer responded to hematopoietic growth factor(s), although the responses of CFU-GM were unchanged. In further studies, anemic cats received suramin, a reverse-transcriptase inhibitor with other diverse effects. Within 4 to 14 days, erythropoiesis improved and up to 1,616 CFU-E were detected per 10(5) marrow mononuclear cells. However, progenitor cells remained infected, suggesting that suramin modulated erythroid differentiation without inhibiting progenitor infection. These observations led to the hypothesis that the gp70 of FeLV-C/Sarma impairs BFU-E differentiation by interference with ligand/receptor interactions or signal transduction pathways unique to erythroid cells. Understanding this mechanism should provide insights into the interactions controlling early erythropoiesis.

Reduction of Prion Infectivity in Packed Red Cells by Separation of Whole Blood and Washing of the Red Cell Fraction.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2890-2890
Author(s):  
Rodrigo Morales ◽  
Kimberley A. Buytaert-Hoefen ◽  
Eric T. Hansen ◽  
Dennis Hlavinka ◽  
Raymond Goodrich ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Whole Blood ◽  
Red Cells ◽  
Cell Fraction ◽  
Health Concern ◽  
Red Cell ◽  
New Variant

Abstract Although prion diseases are rare in humans, the established link between a new variant form of CJD (vCJD) and the consumption of cattle meat contaminated by BSE have raised concerns about a possible outbreak of a large epidemic in the human population. Over the past few years, BSE has become a significant health concern in several countries, and it now seems apparent that vCJD can also be iatrogenically transmitted from human to human by blood transfusion. Exacerbating this state of affairs is the lack of a reliable test to identify individuals incubating the disease during the long and silent period from the onset of infection to the appearance of clinical symptoms. The purpose of this research study was to evaluate the effectiveness of separation of whole blood and washing of the red cell fraction for the removal of infectious scrapie prion protein (PrPSc) from red blood cell (RBC) suspensions. Samples of human, whole blood were spiked with 5 × 106 LD50 263K PrPSc. Analysis of the treated sample supernatants by Western blot revealed that approximately >88% of the PrPSc was removed with the initial plasma expression and the equivalent of 6% was detected in a saline wash (300 mL; 0.9% saline). The final sample of RBCs revealed no detectable levels of PrPSc by Western blots. Further analysis of the treated RBCs using the PMCA assay indicated detectable amounts of PrPSc only after 2 consecutive amplification rounds. Semi-quantitative analysis of PMCA amplification enabled us to estimate that the treated RBCs contained less than 1 × 104 LD50 PrPSc. This corresponded to removal levels exceeding ≥99% of spiked material in whole blood. These in vitro estimations were confirmed by in vivo infectivity studies in a hamster model of disease transmission. Results from in vivo studies displayed significant differences in the incubation periods of the spiked blood inoculated hamsters (100.1 ± 1.7) versus washed RBCs (135.8 ± 6.7). Moreover, a substantial difference in the attack rate (6/15: 40% in washed RBC, versus 13/13: 100% in spiked blood) further indicated a substantial removal of infectious prions. Comparison of this data with results of animals inoculated with different dilutions of infectious material, indicated a >99.94% reduction of infectivity. Washed, packed human red cells produced by this procedure were able to be stored in standard additive solutions (AS-3) for 42 days while still meeting all in vitro blood bank standards for acceptable red cell quality. Conclusion This data suggests that separation of plasma coupled with a simple, low volume wash of red cells may represent an efficient method to remove prions from red blood cell fractions, thus reducing possible infectivity of these products.

Pathophysiology of Thrombocytopenia and Anemia in Mice Lacking Transcription Factor NF-E2

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3037-3047 ◽  
Author(s):  
Jack Levin ◽  
Jin-Peng Peng ◽  
Georgiann R. Baker ◽  
Jean-Luc Villeval ◽  
Patrick Lecine ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Fetal Life ◽  
Wild Type ◽  
Cell Lineages ◽  
Cell Fragments ◽  
Proliferation Potential

Expression of the p45 subunit of transcription factor NF-E2 is restricted to selected blood cell lineages, including megakaryocytes and developing erythrocytes. Mice lacking p45 NF-E2 show profound thrombocytopenia, resulting from a late arrest in megakaryocyte differentiation, and a number of red blood cell defects, including anisocytosis and hypochromia. Here we report results of studies aimed to explore the pathophysiology of these abnormalities. Mice lacking NF-E2 produce very few platelet-like particles that display highly disorganized ultrastructure and respond poorly to platelet agonists, features consistent with the usually lethal hemorrhage in these animals. Thrombocytopenia was evident during fetal life and was not corrected by splenectomy in adults. Surprisingly, fetal NF-E2–deficient megakaryocyte progenitors showed reduced proliferation potential in vitro. Thus, NF-E2 is required for regulated megakaryocyte growth as well as for differentiation into platelets. All the erythroid abnormalities were reproduced in lethally irradiated wild-type recipients of hematopoietic cells derived from NF-E2-null fetuses. Whole blood from mice lacking p45 NF-E2 showed numerous small red blood cell fragments; however, survival of intact erythrocytes in vivo was indistinguishable from control mice. Considered together, these observations indicate a requirement for NF-E2 in generating normal erythrocytes. Despite impressive splenomegaly at baseline, mice lacking p45 NF-E2 survived splenectomy, which resulted in increased reticulocyte numbers. This reveals considerable erythroid reserve within extra-splenic sites of hematopoiesis and suggests a role for the spleen in clearing abnormal erythrocytes. Our findings address distinct aspects of the requirements for NF-E2 in blood cell homeostasis and establish its roles in proper differentiation of megakaryocytes and erythrocytes.

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