Proliferation and Differentiation of Thrombocyte Progenitors In the Liver and the Spleen In Xenopus Laevis Under the Stimulation of Thrombopoietin

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2012-2012
Author(s):  
Yuta Tanizaki ◽  
Ayaka Tahara ◽  
Sayaka Kinoshita ◽  
Motoki Yamauchi ◽  
Mizue Meguro ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Conflicts Of Interest ◽  
Immunohistochemical Analysis ◽  
Human Platelets ◽  
The Body ◽  
Peripheral Blood Cells ◽  
Culture Cells ◽  
Semi Solid

Abstract Abstract 2012 In the biology of thrombopoiesis, several challenging issues such as polyploidy induction, proplatelet formation with endomitotic maturation and tubular cytoplasmic projections, and ability of cell division as reported in human platelets, have not been elucidated sufficiently. Comparative characterization of thrombocyte developments in animals may bring about a new perspective. Characteristics of thrombocyte precursors as megakaryocytes (MKs) and mature thrombocytes in most vertebrates, however, remain poorly defined. Most non-mammalian vertebrates have nucleated and spindle thrombocytes instead of platelets. Since african clawed frog, Xenopus laevis, is one of the most popular species providing various animal models in embryology and physiology, we attempt to establish an adult Xenopus model for analyses of hematopoiesis. We clarified peripheral thrombocytes by various staining methods, and searched immature thrombocytic cells in Xenopus organs. When peripheral blood cells were subjected to acetylcholinesterase staining, thrombocytes in the circulation, i.e. mature thrombocytes were positively identified. The size of elliptical mature thrombocytes was approx. 20.5±0.6 μm by 7.6±1.1 μm in diameters on cytocentrifuge preparations. We produced monoclonal antibody to Xenopus mature thrombocytes (T12) previously. The subsequent flow cytometry with a FACSAria II cell sorter revealed that the proportion of the peripheral T12-positive thrombocytes in lower FSC and SSC ranges were 1.5±0.3% of whole peripheral blood cells, and the expression of Xenopus c-Mpl (xlMpl) mRNA in the sorted cells was detected by RT-PCR. The mRNA expressions of Xenopus TPO (xlTPO) and xlMpl were also detected predominantly in the spleen and the liver, indicating that the sites of thrombocyte progenitor-residing organ and thrombopoietic activity-releasing organ were coincident in adult Xenopus. This resembled the relationship between Xenopus erythropoietin (EPO) and EPO receptor-expressing erythrocytic progenitors, as we have reported (Nogawa-Kosaka et al, 2010, Exp Hematol). Next, immunohistochemical analysis with T12 antibody revealed that thrombocytic cells were localized in sinusoid of the liver and the spleen. We then performed a thrombocytic colony assay in the presence of recombinant xlTPO expressed in E. coli. Hepatic and splenic cells composed of respective 80,000 cells in 1mL were incubated in 35mm dishes at 23°C under 5% CO2 with 0.87% methylcellulose-based semi-solid medium containing 20% FCS and xlTPO (5 ng/ml). The xlTPO-induced colonies derived from the spleen, including T12 positive thrombocytic colonies, emerged after 2 days, and the number reached to 65±2 in the culture (1 mL). The number of liver-derived colonies was smaller than that of spleen-derived ones, indicating that the density of thrombocyte progenitors in Xenopus was higher in the spleen, but the total mass of thrombocyte progenitors in the body is mostly distributed in the liver based on ratio by organ weights. In Xenopus, moderate thrombocytopenia, as well as anemia, was induced by phenylhydrazine (PHZ). The nadir of circulating thrombocyte counts was observed 4 days after PHZ-administration. When we culture cells of the liver or the spleen in the presence of the PHZ-induced thrombocytopenic serum, colonies composed of white cells and red cells were developed, suggesting that multiple or bipotent hematopoietic progenitors existed. When the hepatic cells were stimulated by xlTPO (5 ng/ml) for 2 days in the liquid culture, T12-positive megakaryocytic larger cells with multinucleated spherical shapes (approx. 30 ±3 μm in diameter) appeared, and such cells did not appear under EPO stimulation. On the other hand, the size of megakaryocytic cells derived from the spleen was smaller. Regardless of the origin of the thrombocyte progenitors, the cells stimulated by xlTPO in the liquid cultures expressed mRNAs of c-Mpl, CD41 and Fli-1, demonstrating that thrombocyte progenitors at different development stages resided in the liver and the spleen. It is still a missing piece of the puzzle whether Xenopus thrombocyte progenitors or mature thrombocytes undergo endomitosis to generate higher polyploid cells under the stimulation by TPO; however the unique megakaryocytic cells observed in this study have a clue to reveal the cellular evolution of platelets/MKs. Disclosures: No relevant conflicts of interest to declare.

The Morphology and Cellular Characterization of Thrombocytes in Adult Xenopus laevis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3947-3947
Author(s):  
Takako Ishida ◽  
Miyako Obuchi-Shimoji ◽  
Takeshi Kuribara ◽  
Nami Nogawa ◽  
Tomoyuki Tahara ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Xenopus Laevis ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Structural Characteristics ◽  
Flow Cytometric Analysis ◽  
Peripheral Blood Cells ◽  
Morphological Aspect ◽  
Cell Counts

Abstract In primates and rodents, platelets originate from the bone marrow megakaryocytes through a unique differentiation process with nuclear polyploidization, cytoplasmic maturation and proplatelet formation. In contrast, circulating thrombocytes of most non-mammalian vertebrates are particularly distinctive; the cells are large and nucleated. Adult Xenopus laevis may be an useful non-mammalian model for analyzing dynamic hematopoiesis because they are individually tolerable for time lapse analysis in vivo with sequential blood sampling, whereas classification of cell types has not been established yet. Microstructures of Xenopus thrombocytes observed with electron microscope exhibited structural characteristics largely resembling zebrafish thrombocytes with nucleated spindle cellular features (Thattaliyath et al., Blood 2005), and they had lobulated nuclear chromatin, granules, microparticles and open canalicular system-like-structures as in mammalian megakaryocytes. Since thrombocyte identification based on the morphological aspect was not sufficient, chemical staining with acetylecholinesterase and thiazole orange were performed. Additionally, mice were immunized by Xenopus peripheral blood cells to generate monoclonal antibodies, and two hybridomas producing IgG, respectively T12 and T5, were screened. T12+ (T12 positive) cells were morphologically typical thrombocytes. Flow cytometric analysis revealed that T12+ cells were also positive to anti-human GpIIb/IIIa polyclonal antibodies, and approximately 2-3% of whole peripheral blood cells were T12+/GpIIb/IIIa+ that distributed in FSClow/SSClow fraction. When T12 was injected into Xenopus to deplete T12+ cells in vivo, the detectable level of T12 in the circulation lasted for more than several weeks. Peripheral thrombocyte counts predominantly began to decrease immediately and reached their nadir at day 3, but white blood cell counts were not changed. RNA-rich blood cells considered as younger cells were then increasingly appeared, and finally the cell counts recovered to normal levels at day 10–15, indicating that in vivo depletion of T12+ cells induced thrombopoiesis and/or release of mature thrombocytes from the pool. T5 recognizing cells were classified into two populations by immunostaining and flow cytometry; T5+/GpIIb/IIIa+ cells were morphologically thrombocytic as the cells recognized by T12, while T5+/GpIIb/IIIa− cells were spherical and similar appearance to lymphocytic cells. These observations raised some possibilities e.g.; antigen of T5 was a membrane protein common to both lymphocytes and thrombocytes, or T5+/GpIIb/IIIa− cells were thrombocyte progenitors at earlier development stage than T12+/GpIIb/IIIa+ cells. Nevertheless only a few percent of T12+ and T5+ cells resided in peripheral blood, immunostaining revealed that the proportions of T12+/T5+ and T5+ cells in spleen were 10% and 70%, and T12+/T5+ and T5+ cells in liver were 5% and 20%, respectively. These suggest that spleen is predominantly involved in thrombopoiesis and/or thrombocyte storage in adult Xenopus. As T12 and T5 can be used successfully in flow cytometry and magnetic cell sorting, they should contribute us directly to elucidate the origin of circulating Xenopus thrombocytes and their cellular development process.

Hematological Changes in Cold-Acclimated Xenopus laevis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4212-4212
Author(s):  
Yuko Kuramochi ◽  
Nami Nogawa ◽  
Takako Ishida ◽  
Takafumi Watanabe ◽  
Nobuyoshi Kosaka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Xenopus Laevis ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Environmental Temperature ◽  
Peripheral Blood Cells ◽  
Transient Phase ◽  
Hematopoietic Regulation ◽  
Hematological Changes

Abstract While hematopoiesis in individuals is strictly regulated for maintenance of homeostasis, it has been reported that the numbers of peripheral blood cells are modulated in response to environmental temperature in vertebrates including hamsters, rats, squirrels, dogs, and bullfrogs. To date, the physiological and molecular mechanisms have not been elucidated yet. Amphibians are poikilothermic vertebrates exposed to various fluctuations of environmental conditions; therefore they need to exert their capacities to acclimate to such changes. Additionally numerous studies have demonstrated a measurable metabolic reduction in the metabolic rate of cold-acclimated frogs. We examined hematological changes in response to environmental temperature in an aquatic amphibian, Xenopus laevis. Frogs initially maintained at 25°C were acclimated to 10°C, and hematological changes were observed. The numbers of erythrocytes, leukocytes and thrombocytes gradually reduced as the transient phase by 4 weeks, and subsequently reached the steady-state that sustained for more than 4 months. Whereas the reduction in the numbers of white blood cells and thrombocytes were moderate, the number of erythrocytes and the level of hemoglobin at nadir were remarkably low (approximately 40% of the initial values). It is known that oxygen levels may reduce in ice-cold water, and cold-acclimated animals therefore tolerate prolonged severe hypoxia; nevertheless cold-acclimated Xenopus exhibited severe erythrocytopenia. In addition, morphological change of peripheral blood cells and hematopoietic tissues (liver, spleen, kidney, and bone marrow) were examined. There were no remarkable cellular changes in cellular size and shape. However, increased numbers of mature erythrocytes were observed in the bone marrow of the steady state cold-acclimated Xenopus, while mature erythrocytes were not found in the bone marrow in Xenopus at 25 °C. This cold-temperature-induced pancytopenia was reversible when the temperature was put back to 25°C, as all of blood cell counts returned to the normal levels within 4 weeks in a reverse fashion as the transient phase of cold-acclimation. During the recovery phase, immature erythrocytes that were scarcely existed in the normal peripheral blood appeared in the circulation, suggesting that erythrocytes were newly produced at 25 °C after prolonged exposure to cold temperature. The possible explanations for the reduction in the numbers of circulating peripheral blood cells might be due to a number of various reasons such as reduced productions of hamatopoietic progenitors and/or related cytokines, alternation in the storage capacities and/or the life span of blood cells, and systemic suspension of normal activities. To compare the lifespan of erythrocytes between normal and cold-acclimated Xenopus, erythrocytes were covalently labeled with biotin. The surviving biotinylated erythrocytes in the circulation were quantitatively detected as avidin-biotin complex by microscopy and flowcytometry. Furthermore expression levels of several genes responsible for the hematopoietic regulation were comparatively examined. The cold-acclimated Xenopus model developed here may allow for a valuable approach aiming at exploring undiscovered systems in hematopoietic regulation.

The Ryk Receptor Regulates Hematopoietic Stem and Progenitor Cell Proliferation and Their Sensitivity To Myeloablative Agents

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 796-796
Author(s):  
Benjamin Povinelli ◽  
Michael Nemeth
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Molecular Mechanisms ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Peripheral Blood Cells ◽  
Hematopoietic Stem ◽  
Marrow Cells

Abstract The molecular mechanisms that control the balance between quiescence and proliferation of hematopoietic stem and progenitor cells (HSPCs) are critical for maintaining life-long hematopoiesis. In a recent study (Povinelli, et al. Stem Cells, In Press, 2013) we demonstrated that the Wnt5a ligand inhibits HSPC proliferation through a functional interaction with a non-canonical Wnt ligand receptor termed Related to Receptor Tyrosine Kinase (Ryk). Expression of Ryk on HSPCs in vivo was associated with a decreased rate of proliferation. Following treatment with fluorouracil (5-FU), the percentage of Ryk+ HSPCs increased at the expense of Ryk-/low HSPCs. Based on these data, we hypothesized that one function of the Ryk receptor is to protect HSPCs from the effects of myeloablative agents. To test this hypothesis, we injected 6-8 week old C57BL/6 mice with 150 mg/kg of 5-FU and analyzed bone marrow 48 hours later for the presence of apoptotic HSPCs, defined as lineage negative (Lin-), Sca-1+, CD48- cells positive for active caspase-3. There was a 2.5-fold decrease in the percentage of apoptotic Ryk+ HSPCs (12.9 ± 1.7%) compared to Ryk-/low HSPCs (32.4 ± 5.3%, p < 0.001, n = 3). To test whether this effect was limited to 5-FU, we performed a similar study in which we irradiated C57BL/6 mice with 3 cGy of total body irradiation (TBI) and analyzed bone marrow 72 hours later for apoptotic HSPCs (for this experiment, defined by a Lin-, c-kit+, Sca-1+, CD150+, CD48- immunophenotype or LSK, SLAM). Comparable to the effects of 5-FU, there was a significant 3.0-fold reduction in the percentage of apoptotic Ryk+ HSPCs (3.1 ± 0.2%) compared to Ryk-/low HSPCs (9.2 ± 1.5%, p < 0. 001, n = 3) in mice receiving 3 cGy TBI. These results demonstrated an association between Ryk expression and survival of HSPCs following myeloablative injury. To determine whether in vivo targeting of the Ryk receptor would increase the sensitivity of HSPCs to myeloablative injury, we utilized a neutralizing rabbit anti-Ryk antibody (α-Ryk). We injected C57BL/6 mice with 5 mg/kg α-Ryk or rabbit IgG isotype for 2 consecutive days. Twenty-four hours after the second dose, we determined the frequency and cell cycle status of LSK SLAM cells. Treatment with α-Ryk significantly increased the percentage of LSK SLAM cells in the S/G2/M phases compared to control (α-Ryk: 17.8 ± 2.2%; isotype IgG: 11.6 ± 2.7%, p < 0.05, n = 3). This was associated with a decrease in the percentage of LSK, SLAM cells in G1 following treatment with α-Ryk (α-Ryk: 40.5 ± 3.2%, isotype IgG: 51.3 ± 2.2; p < 0.01, n = 3). The percentage of G0 LSK SLAM cells was unchanged (α-Ryk: 37.9 ± 2.6, isotype IgG: 35.7 ± 3.1% n = 3) indicating that inhibiting Ryk promoted the exit of LSK SLAM cells from G1. Treatment with α-Ryk also increased the percentage of whole bone marrow cells expressing the LSK SLAM phenotype by 1.4-fold compared to controls (p < 0.05, n = 3). To determine if α-Ryk treatment altered HSPC function, we transplanted whole bone marrow cells from C57BL/6 mice treated with two days of α-Ryk or isotype IgG at a 1:1 ratio with whole bone marrow from untreated Ubc-GFP transgenic mice into lethally irradiated B6.SJL mice. Four weeks after transplant, we analyzed peripheral blood cells for the percentage of CD45.2+ GFP- cells. There was no difference in engraftment by transplanted bone marrow cells from mice treated with α-Ryk or isotype IgG (α-Ryk: 61.6 ± 6.1% n = 4, isotype IgG: 52.8 ± 13.6%, n = 5), indicating that the neutralizing antibody does not inhibit short-term HSPC function on its own. We then tested whether blocking Ryk function resulted in greater sensitivity of HSPCs to 5-FU. We treated B6.SJL mice with 5 mg/kg α-Ryk or isotype IgG for 2 consecutive days, followed by 150 mg/kg of 5-FU. Forty-eight hours after 5-FU treatment, we transplanted 2x106 C57BL/6 whole bone marrow cells into treated B6.SJL mice without additional conditioning. Four weeks after transplant, we determined the percentage of donor-derived CD45.2+ peripheral blood cells. Treatment of recipient mice with α-Ryk prior to 5-FU treatment resulted in increased engraftment of donor bone marrow by 3.6-fold compared to isotype (p < 0.05, n = 5), suggesting that inhibition of Ryk resulted in increased elimination of host HSPCs by 5-FU. Collectively, these data suggest a model in which inhibition of the Ryk receptor results in increased proliferation of HSPCs, rendering them more sensitive to the effects of myeloablative agents such as chemotherapy or TBI. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Eight-year longitudinal study of whole blood gene expression profiles in individuals undergoing long-term medical follow-up

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshio Sakai ◽  
Alessandro Nasti ◽  
Yumie Takeshita ◽  
Miki Okumura ◽  
Shinji Kitajima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
The Body ◽  
Peripheral Blood Cells ◽  
Peripheral Tissues ◽  
Altered Gene

AbstractBlood circulates throughout the body via the peripheral tissues, contributes to host homeostasis and maintains normal physiological functions, in addition to responding to lesions. Previously, we revealed that gene expression analysis of peripheral blood cells is a useful approach for assessing diseases such as diabetes mellitus and cancer because the altered gene expression profiles of peripheral blood cells can reflect the presence and state of diseases. However, no chronological assessment of whole gene expression profiles has been conducted. In the present study, we collected whole blood RNA from 61 individuals (average age at registration, 50 years) every 4 years for 8 years and analyzed gene expression profiles using a complementary DNA microarray to examine whether these profiles were stable or changed over time. We found that the genes with very stable expression were related mostly to immune system pathways, including antigen cell presentation and interferon-related signaling. Genes whose expression was altered over the 8-year study period were principally involved in cellular machinery pathways, including development, signal transduction, cell cycle, apoptosis, and survival. Thus, this chronological examination study showed that the gene expression profiles of whole blood can reveal unmanifested physiological changes.

scholarly journals THE PECULIARITIES OF SOME INDICES OF PERIPHERAL BLOOD OF FOREIGN STUDENTS

2019 ◽  
Vol 9 (1) ◽  
pp. 20-25
Author(s):  
Oxana Anfinogenova ◽  
Irina Lisova ◽  
Aiyshat Elkanova ◽  
Sergey Kubanov ◽  
Vasily Anfinogenov ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Blood Cells ◽  
External Environment ◽  
Test System ◽  
The Body ◽  
Peripheral Blood Cells ◽  
North Caucasus ◽  
Blood Indices ◽  
Software Complex ◽  
The North

The aim of the research is: to study the morphofunctional characteristics of the peripheral blood cells of healthy young people of the same age group, taking into account the dependence on the ecological and biogeochemical factors of the external environment of the region of residence and to identify the physiological mechanisms underlying adaptation to the external environment. Materials and methods. there were examined 125 students studied at the North Caucasus Federal University at the age of 18–21. For the quantitative evaluation of peripheral blood cells, 15 laboratory parameters were determined on the MEDONIK M-SERIES hematology analyzer. Leukocyte analysis was performed on the MECOS-C3 hardware-software complex. Results. The analysis of peripheral blood indices revealed significant shifts in adaptation processes in the direction of tension in the group of Indian students (P <0.01) and less critical changes in the compensatory-adaptive mechanisms of the body in the group of students from Tajikistan (P <0.05). Conclusion. As a result of the study, new data have been obtained indicating a different spectrum of adaptive reactions of students, which allows the use of peripheral blood as a test system for assessing the influence of damaging environmental factors.

scholarly journals Asparaginase Immune Complexes Detectable after Asparaginase-Induced Hypersensitivities Activate Basophils Via FcγRIII

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5210-5210
Author(s):  
Sanjay Rathod ◽  
Fred D Finkelman ◽  
Christian Fernandez
Keyword(s):  
Flow Cytometry ◽  
Immune Complexes ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Lymphoblastic Leukemia ◽  
Peripheral Blood Cells ◽  
Dependent Manner ◽  
Igg Antibodies

Abstract Background: Asparaginase (ASNase) is an important chemotherapeutic agent for the treatment of acute lymphoblastic leukemia (ALL). However, the development of anti-ASNase IgG antibodies are frequent, can neutralize the enzyme activity of ASNase, and can increase the risk of ALL relapse. Nevertheless, the role of anti-ASNase IgG antibodies on the onset of ASNase-induced hypersensitivity reactions is unknown, but likely require the formation of ASNase immune complexes (ICs) to activate cells involved in hypersensitivities due to the low binding affinity of the Fcγ receptor for the IgG immunoglobulin. Objective: To detect plasma ASNase ICs after the onset of ASNase hypersensitivities and to demonstrate that binding of ASNase ICs to peripheral blood cells, and the subsequent immune cell activation, is FcγRIII-dependent. Methods: Mice were sensitized to native E.coli ASNase using aluminum hydroxide adjuvant. ICs prepared using the plasma of sensitized mice were precipitated using polyethylene glycol to remove free ASNase and anti-ASNase IgG. ICs were detected by flow cytometry using APC labeled ASNase and protein G beads, characterized by dynamic light scattering and TEM, and the binding properties of ASNase ICs or free ASNase were determined by flow cytometry using non-sensitized and sensitized peripheral murine blood cells and the anti-IgE and/or anti-FcγRIIβ/III blocking mAb. Activation of basophils, which can occur in an IgE- or FcγRIII-dependent manner, was determined ex vivo by measuring changes in CD200R1 or CD200R3 expression after incubating peripheral blood cells with ASNase or ASNase ICs. Results: ASNase ICs were detected after the onset of ASNase hypersensitivities in mice. ASNase ICs formed ex vivo at high anti-ASNase IgG1 concentrations, bound to naïve peripheral blood cells (e.g., neutrophils macrophage/monocytes, and basophils), and activated basophils in an FcγRIII-dependent manner. In contrast, basophil binding and activation by free ASNase was IgE- and not FcγRIII-dependent. Conclusion: Our data indicate that ASNase sensitized mice form ICs after drug administration and can activate basophils via the FcγRIII receptor in mice, whereas the binding and activation by free ASNase occurs via cell-associated IgE. Our study suggests that ASNase ICs can contribute to the onset and severity of ASNase hypersensitivity. Disclosures No relevant conflicts of interest to declare.

Receptor Mediated Binding of the Fibrinolytic Components, Plasminogen and Urokinase, to Peripheral Blood Cells

1987 ◽  
Vol 58 (03) ◽  
pp. 936-942 ◽  
Author(s):  
Lindsey A Miles ◽  
Edward F Plow
Keyword(s):  
T Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Binding Sites ◽  
Blood Cells ◽  
High Capacity ◽  
Red Cells ◽  
Peripheral Blood Cells ◽  
Cellular Functions ◽  
Fibrinolytic Proteins

SummaryGlu-plasminogen binds to platelets; the monocytoid line, U937, and the human fetal fibroblast line, GM1380 bind both plasminogen and its activator, urokinase. This study assesses the interaction of these fibrinolytic proteins with circulating human blood cells. Plasminogen bound minimally to red cells but bound saturably and reversibly to monocytes, granulocytes and lymphocytes with apparent Kd values of 0.9-1.4 μM. The interactions were of high capacity with 1.6 to 49 × 105 sites/cell and involved the lysine binding sites of plasminogen. Both T cells and non-rosetting lymphocytes and two B cell lines saturably bound plasminogen. Urokinase bound saturably to gianulocytes, monocytes, non-rosetting lymphocytes and a B cell line, but minimally to T cells, platelets and red cells. Therefore, plasminogen binding sites of high capacity, of similar affinities, and with common recognition specificities are expressed by many peripheral blood cells. Urokinase receptors are also widely distributed, but less so than plasminogen binding sites. The binding ol plasminogen and/ or urokinase to these cells may lead to generation of cell- associated proteolytic activity which contributes to a variety of cellular functions.

scholarly journals RNA Sequencing of Human Peripheral Blood Cells Indicates Upregulation of Immune-Related Genes in Huntington's Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Miguel A. Andrade-Navarro ◽  
Katja Mühlenberg ◽  
Eike J. Spruth ◽  
Nancy Mah ◽  
Adrián González-López ◽  
...  
Keyword(s):  
Gene Expression ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Trinucleotide Repeat ◽  
Neurodegenerative Disorder ◽  
Gene Expression Signature ◽  
Interferon Response ◽  
Peripheral Blood Cells

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the Huntingtin gene. As disease-modifying therapies for HD are being developed, peripheral blood cells may be used to indicate disease progression and to monitor treatment response. In order to investigate whether gene expression changes can be found in the blood of individuals with HD that distinguish them from healthy controls, we performed transcriptome analysis by next-generation sequencing (RNA-seq). We detected a gene expression signature consistent with dysregulation of immune-related functions and inflammatory response in peripheral blood from HD cases vs. controls, including induction of the interferon response genes, IFITM3, IFI6 and IRF7. Our results suggest that it is possible to detect gene expression changes in blood samples from individuals with HD, which may reflect the immune pathology associated with the disease.

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