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Matías Grodzielski, Nora P Goette, Ana C Glembotsky, M Constanza Baroni Pietto, Santiago P Méndez-Huergo, Marta S Pierdominici, Verónica S Montero, Gabriel A Rabinovich, Felisa C Molinas, Paula G Heller, Paola R Lev, Rosana F Marta
Mechanisms leading to low platelet count in immune thrombocytopenia (ITP) involves both decreased production and increased destruction of platelet. However, the contribution of these pathologic mechanisms to clinical outcome of individual patients is uncertain. Here we evaluated different pathogenic mechanisms including in vitro megakaryopoiesis, platelet/megakaryocyte (MK) desialylation and MK apoptosis, and compared these effects with thrombopoyesis and platelet apoptosis in the same cohort of ITP patients...
February 18, 2019: Scientific Reports
Kenneth Kaushansky, Huichun Zhan
The hematopoietic niche is composed of endothelial cells, mesenchymal stromal cells of several types, and megakaryocytes, and functions to support the survival, proliferation, and differentiation of normal hematopoietic stem cells (HSCs). An abundance of evidence from a range of hematological malignancies supports the concept that the niche also participates in the pathogenesis of malignant hematopoiesis, differentially supporting malignant stem or progenitor cells over that of normal blood cell development...
February 14, 2019: Annals of the New York Academy of Sciences
Alessandra Balduini
No abstract text is available yet for this article.
February 14, 2019: Blood
Georges J M Maestroni
Hematopoiesis produce every day billions of blood cells and takes place in the bone marrow (BM) by the proliferation and differentiation of hematopoietic stem cells (HSC). HSC are found mainly adjacent to the BM vascular sinusoids where endothelial cells and mesenchimal stromal cells promote HSC maintenance by producing a variety of factors. Other cell types that regulate HSC niches include sympathetic nerves, non-myelinating Schwann cells and a variety of mature hematopoietic cells such as macrophages, neutrophils, and megakaryocytes...
February 14, 2019: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Catherine Strassel, Maria M Magiera, Arnaud Dupuis, Morgane Batzenschlager, Agnès Hovasse, Irina Pleines, Paul Guéguen, Anita Eckly, Sylvie Moog, Léa Mallo, Quentin Kimmerlin, Stéphane Chappaz, Jean-Marc Strub, Natarajan Kathiresan, Henri de la Salle, Alain Van Dorsselaer, Claude Ferec, Jean-Yves Py, Christian Gachet, Christine Schaeffer-Reiss, Benjamin T Kile, Carsten Janke, François Lanza
During platelet biogenesis, microtubules (MTs) are arranged into submembranous structures (the marginal band) that encircle the cell in a single plane. This unique MT array has no equivalent in any other mammalian cell, and the mechanisms responsible for this particular mode of assembly are not fully understood. One possibility is that platelet MTs are composed of a particular set of tubulin isotypes that carry specific posttranslational modifications. Although β1-tubulin is known to be essential, no equivalent roles of α-tubulin isotypes in platelet formation or function have so far been reported...
February 2019: Life science alliance
Isabella Massimi, Laura Alemanno, Maria Luisa Guarino, Raffaella Guerriero, Massimo Mancone, Andrea Ceccacci, Luigi Frati, Dominick J Angiolillo, Fabio M Pulcinelli
Chronic treatment with aspirin in healthy volunteers (HVs) is associated with recovery of adenosine diphosphate (ADP)-induced platelet activation. The purinergic P2Y1 receptor exerts its effects via a Gq -protein, which is the same biochemical pathway activated by thromboxane-A2 receptor. We hypothesized that recovery of ADP-induced platelet activation could be attributed to increased P2Y1 expression induced by chronic aspirin exposure. We performed a multi-phase investigation which embraced both in vitro and in vivo experiments conducted in (1) human megakaryoblastic DAMI cells, (2) human megakaryocytic progenitor cell cultures, (3) platelets obtained from HVs treated with aspirin and (4) platelets obtained from aspirin-treated patients...
February 13, 2019: Thrombosis and Haemostasis
Saleh Rachidi, Maneet Kaur, Tim Lautenschlaeger, Zihai Li
Cancer is a chronic inflammatory state which is often associated with increased platelet counts. Cancer cells induce thrombopoiesis and activate platelets, which in turn facilitate cancer invasion and metastasis. In this study, we investigate the correlation between platelet counts with each of stage and overall survival in melanoma. This is a retrospective cohort study of 642 melanoma patients diagnosed or treated at a tertiary medical center between 2000 and 2016. Multivariable analysis adjusted for age, sex, stage, and treatment modality...
February 13, 2019: Platelets
Sandra Pinho, Paul S Frenette
The haematopoietic stem cell (HSC) microenvironment in the bone marrow, termed the niche, ensures haematopoietic homeostasis by controlling the proliferation, self-renewal, differentiation and migration of HSCs and progenitor cells at steady state and in response to emergencies and injury. Improved methods for HSC isolation, driven by advances in single-cell and molecular technologies, have led to a better understanding of their behaviour, heterogeneity and lineage fate and of the niche cells and signals that regulate their function...
February 11, 2019: Nature Reviews. Molecular Cell Biology
Paola Maroni
Bone is the primary site where some cancers develop secondary growth, particularly those derived from breast and prostate tissue. The spread of metastasis to distant sites relies on complex mechanisms by which only cells endowed with certain characteristics are able to reach secondary growth sites. Platelets play a pivotal role in tumour growth, by conferring resistance to shear stress to the circulating tumour cells and protection against natural killer cell attack. Mature polyploid megakaryocytes (MKs) reside in close proximity to the vascular sinusoids of bone marrow, where their primary function is to produce platelets...
February 8, 2019: Cells
Jinxue Zhang, Ran Zhuang, Xuexin Zhang, Wei Hu, Kun Cheng, Dongxu Jiang, Shen Shen, Yun Zhang, Yong Ding, Yuan Zhang
This study was conducted to investigate the effect of CD226 on the differentiation, activation, and polyploidization of megakaryocytes (MKs) and explore the potential mechanism. Dami (megakaryocyte line) cell maturation was induced by phorbol 12-myristate 13-acetate. CD226 was silenced by infection with a CD226-specific shRNA lentiviral vector. The mRNA level of CD226 was detected by qRT-PCR. The expressions of Dami cells surface CD226, MK specific markers CD41 and CD62P, and DNA ploidy in Dami cells and CD226 knockdown (KD) cells were evaluated by flow cytometry...
February 6, 2019: Molecular Immunology
Ahmed Saif Hilal Al-Amri, Waleed Al-Marzooqi, Mohammed Al-Abri, Eugene H Johnson
An ultrastructural study on the platelets from peripheral blood samples from 20 healthy adult Arabian oryx (Oryx leucocoryx) was performed. Characteristic was the extreme polymorphism of both the platelets, as well as their alpha granules. They vary in size from 100 to 800 nm in diameter and their numbers typically are less than those reported for humans and other animal species. Also, the alpha granules in contrast to those of humans and animals, such as the Arabian tahr, do not have nucleoids. Typically, the oryx platelets exhibit only 1-2 electron-dense bodies per cell and they lack an open canalicular system...
February 7, 2019: Anatomia, Histologia, Embryologia
Alessandro Malara, Cristian Gruppi, Vittorio Abbonante, Daniele Cattaneo, Luigi De Marco, Margherita Massa, Alessandra Iurlo, Umberto Gianelli, Carlo L Balduini, Maria E Tira, Andrès F Muro, Anil K Chauhan, Vittorio Rosti, Giovanni Barosi, Alessandra Balduini
The fibronectin EDA isoform (EDA FN) is instrumental in fibrogenesis but, to date, its expression and function in bone marrow (BM) fibrosis have not been explored. We found that mice constitutively expressing the EDA domain (EIIIA+/+ ), but not EDA knockout mice, are more prone to develop BM fibrosis upon treatment with the thrombopoietin (TPO) mimetic romiplostim (TPOhigh ). Mechanistically, EDA FN binds to TLR4 and sustains progenitor cell proliferation and megakaryopoiesis in a TPO-independent fashion, inducing LPS-like responses, such as NF-κB activation and release of profibrotic IL-6...
February 7, 2019: Journal of Experimental Medicine
Seema Bhatlekar, Indranil Basak, Leonard C Edelstein, Robert A Campbell, Cory R Lindsey, Joseph E Italiano, Andrew S Weyrich, Jesse W Rowley, Matthew T Rondina, Martha Sola-Visner, Paul F Bray
Apoptosis is a recognized limitation for generating large numbers of megakaryocytes in culture. The responsible apoptosis genes have been rigorously studied in vivo in mice, but are poorly characterized in human culture systems. As CD34+ cells isolated from human umbilical vein cord blood were differentiated into megakaryocytes in culture, two distinct cell populations were identified by flow cytometric forward and side scatter: larger size, lower granularity and smaller size, higher granularity. The larger size, lower granularity cells were CD41aHighCD42aHighphosphatidylserineLow, had an electron microscopic morphology similar to mature bone marrow megakaryocytes, developed proplatelets, and displayed a signaling response to platelet agonists...
February 7, 2019: Haematologica
Wenwen Fu, Jichun Wang, Hong Jiang, Xiaorong Hu
Platelet, apart from its classic role of homeostasis, serves also as a crucial immune cell component that contributes to the aggravation of atherosclerosis. It has been reported that myocardial infarction (MI) triggers leukocytosis in the bone marrow and spleen, which accelerates post-MI atherosclerosis. However, it remains unclear whether thrombopoiesis is also enhanced after MI. Here, using flow cytometry and bone marrow whole-mount immunofluorescence staining combined with three-dimensional (3D) reconstruction, we for the first time demonstrated an enhanced thrombopoiesis and megakaryopoiesis in a mouse model of coronary artery ligation as a mimic of MI...
February 4, 2019: Biochemical and Biophysical Research Communications
Robert A Campbell, Hansjorg Schwertz, Eugenio D Hottz, Jesse W Rowley, Bhanu Kanth Manne, A Valance Washington, Robert Hunter-Mellado, Neal D Tolley, Miles Christensen, Alicia S Eustes, Emilie Montenont, Seema Bhatlekar, Cassandra H Ventrone, Beth D Kirkpatrick, Kristen K Pierce, Stephen S Whitehead, Sean A Diehl, Paul F Bray, Guy A Zimmerman, Yasuhiro Kosaka, Patricia T Bozza, Fernando A Bozza, Andrew S Weyrich, Matthew T Rondina
Evolving evidence indicates that platelets and megakaryocytes (MKs) have unexpected activities in inflammation and infection; but whether viral infections upregulate biologically active, anti-viral immune genes in platelets and MKs is unknown. We examined anti-viral immune genes in these cells in dengue and influenza infections, viruses that are global public health threats. Using complementary biochemical, pharmacological, and genetic approaches, we examined the regulation and function of interferon induced transmembrane protein 3 (IFITM3), an anti-viral immune effector gene not previously studied in human platelets and MKs...
February 5, 2019: Blood
Kanako Wakahashi, Kentaro Minagawa, Yuko Kawano, Hiroki Kawano, Tomohide Suzuki, Shinichi Ishii, Akiko Sada, Noboru Asada, Mari Sato, Shigeaki Kato, Kotaro Shide, Kazuya Shimoda, Toshimitsu Matsui, Yoshio Katayama
Myelofibrosis in myeloproliferative neoplasms (MPNs) with mutations such as JAK2V617F is an unfavorable sign for uncontrollable disease progression in the clinic and is complicated with osteosclerosis whose pathogenesis is largely unknown. Because several studies have revealed that macrophages are indispensable supporter for bone forming osteoblasts, we speculated that macrophages might play a significant role in the proliferation of collagen-producing myofibroblasts in marrow fibrotic tissues. Here, we show that myelofibrosis critically depends on macrophages whose differentiation is skewed by vitamin D receptor (VDR) signaling...
February 4, 2019: Blood
Xu-Ling Luo, Jin-Yong Jiang, Zhen Huang, Lin-Xi Chen
Platelets, developed from megakaryocytes, are characterized by anucleate and short-life span hemocyte in mammal vessel. Platelets are very important in the cardiovascular system. Studies indicate the occurrence of autophagy platelets and megakaryocytes. Moreover, abnormal autophagy decreases the number of platelets and suppresses platelet aggregation. In addition, mitophagy, as a kind of selective autophagy, could inhibit platelet aggregation under oxidative stress or hypoxic, whereas promote platelet aggregation after reperfusion...
February 4, 2019: Journal of Cellular Physiology
Cai Yuan, Angela M Boyd, Jan Nelson, Rushang D Patel, Juan C Varela, Steven C Goldstein, Sarfraz Ahmad, Xiang Zhu, Shahram Mori
Thrombocytopenia after Allogeneic hematopoietic stem cell transplantation (Allo-SCT) can pose significant problems in management of patients. Eltrombopag is a small molecule, thrombopoietin receptor agonist (TPO-R) which has been approved for use in immune thrombocytopenia purpura (ITP) and aplastic anemia; but its use after the Allo-SCT is limited. We treated 13 patients with Eltrombopag for poor platelet engraftment without evidence of relapse at the time of initiation between 2014-2017. Six patient had primary platelet engraftment failure and seven patients had secondary platelet engraftment failure...
January 30, 2019: Biology of Blood and Marrow Transplantation
Muhammad Yassin, Nasma Aqaqe, Abed Alkader Yassin, Peter van Galen, Eitan Kugler, Bradley E Bernstein, Maya Koren-Michowitz, Jonathan Canaani, Arnon Nagler, Eric R Lechman, John E Dick, Erno Wienholds, Shai Izraeli, Michael Milyavsky
Acute leukemia is an aggressive blood malignancy with low survival rates. A high expression of stem-like programs in leukemias predicts poor prognosis and is assumed to act in an aberrant fashion in the phenotypically heterogeneous leukemia stem cell (LSC) population. A lack of suitable genome engineering tools that can isolate LSCs based on their stemness precludes their comprehensive examination and full characterization. We hypothesized that tagging endogenous stemness-regulatory regions could generate a genome reporter for the putative leukemia stemness-state...
January 31, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Eduardo I Cardenas, Ricardo Gonzalez, Keegan Breaux, Qi Da, Berenice A Gutierrez, Marco A Ramos, Rodolfo A Cardenas, Alan R Burns, Rolando E Rumbaut, Roberto Adachi
Platelet degranulation, a form of regulated exocytosis, is crucial for hemostasis and thrombosis. Exocytosis in platelets is mediated by SNARE proteins, and in most mammalian cells this process is controlled by Munc18 (mammalian homolog of C. elegans uncoordinated gene 18) proteins. Platelets express all Munc18 paralogs (Munc18‑1, ‑2, and ‑3), but their roles in platelet secretion and function have not been fully characterized. Using Munc18‑1, ‑2, and ‑3 conditional knockout mice, here we deleted expression of these proteins in platelets and assessed granule exocytosis...
January 29, 2019: Journal of Biological Chemistry
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