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Mo Yang - One of the best experts on this subject based on the ideXlab platform.

  • Effect of monoamine neurotransmitter on Megakaryocytopoiesis and platelet functions
    Zhongguo shi yan xue ye xue za zhi, 2014
    Co-Authors: Hui-ying Shu, Mo Yang
    Abstract:

    The nervous system directly regulates immunity through neurotransmitter receptors expressed on immune cells to participate in host defense and body reparation. Expression of neurotransmitter receptors on blood cells provides important evidence for a direct functional link between the nervous and hematopoietic systems. Our previous studies showed that 5-hydroxytryptamine, as a monoamine neurotransmitter, plays an important role in regulating Megakaryocytopoiesis. This review summarizes recent findings of the effect of monoamine neurotransmitter on Megakaryocytopoiesis and platelet function, focusing on the receptor expression on hematopoietic stem cells, megakaryocytes/platelets and their functions in order to explore the intrinsic relation of nervous system and hematopoietic system. Based on the existing research results, we find that the monoamine neurotransmitter participates in regulation of Megakaryocytopoiesis, and affects on aggregation and functions activation of platelets. Moreover, it has a close link with the specific regulatory factor of Megakaryocytopoiesis-TPO. Thus those results also support the "brain-bone marrow-blood-axis" viewpoint of some researchers. At present, the study of the nervous system regulating hematopoiesis is still in its infancy, the exact mechanism remains to be further studied.

  • The Molecular Mechanisms of Serotonin in the Regulation of Megakaryocytopoiesis and TPO Production
    Blood, 2012
    Co-Authors: Mo Yang, Fanyi Meng, Bin Xiao, Beng H Chong
    Abstract:

    Abstract 3347 We have reported that serotonin (5-HT) show a promoting effect on cord blood CD34+ stem/progenitor cells (Yang et al, Stem Cells 2007). We also demonstrated that serotonin enhances murine megakaryopoiesis via 5-HT2 receptors (Yang et al. Blood Coagul Fibrinol 1996). In this present study, we explored how serotonin regulated human Megakaryocytopoiesis, proplatelet formation, and thrombopoietin (TPO) production. Our results indicated that serotonin significantly promoted human CFU-MK formation and reduced apoptosis in megakaryocytes through phosphorylation of Akt. These effects were attenuated by addition of ketanserin, a 5-HT2 receptor inhibitor. In addition, serotonin was able to stimulate the F-actin reorganization in megakaryocytes through activating the p-Erk1/2 expression. Bone marrow mesenchymal stromal cells (MSCs) are important in regulating Megakaryocytopoiesis through stimulating release of thrombopoietic growth factor, such as TPO. Our studies suggested that when activated by serotonin, bone marrow MSCs were induced to release significant amount of TPO by q-PCR, ELISA and cytokine-array assays. Our findings demonstrated an important role of serotonin played on Megakaryocytopoiesis. This effect was likely mediated via 5HT2 receptors with subsequent activation of Akt and Erk 1/2 phosphorylation, which led to survival of megakaryocytes and proplatelet formation. Serotonin also stimulated TPO released from MSCs, which indirectly promoted megakaryopoiesis. In present studies, we have demonstrated a positive “feed-back” control loop between MK-derived granule- serotonin and Megakaryocytopoiesis. These findings improved our knowledge on Megakaryocytopoiesis regulation and provided new clues on identifying novel thrombopoietic agents. It also deepened our understandings on how TPO production is regulated. Disclosures: No relevant conflicts of interest to declare.

  • The effect of 5-hydroxtryptamine on the regulation of Megakaryocytopoiesis.
    Hematology, 2006
    Co-Authors: Yuan-sheng Liu, Mo Yang
    Abstract:

    5-Hydroxtryptamine (5-HT, serotonin) has been recognized not only as a neurotransmitter and vasoactive agent, but also as a growth factor. 5-HT mainly binds to 5-HT2 receptors or 5-HT1 receptors on cell surfaces to stimulate cell proliferation through Ras or MAPK (mitogen-activated protein kinase) pathways in many cell types. It has been reported that 5-HT stimulates Megakaryocytopoiesis via 5-HT receptors (5-HTR). The possible mechanism by which 5-HT regulates the proliferation and differentiation of megakaryocytes (MK) is discussed in this review article. In early stages of Megakaryocytopoiesis, 5-HT may bind to 5-HT2B receptors on MK to promote their proliferation and differentiation. In the late stages, 5-HT may be involved in platelet release by inducing nitric oxide (NO) synthesis via 5-HT2A receptors. 5-HT can also antagonize the apoptotic effect induced by thrombospondin-1 (TSP-1) which is a platelet alpha-granule protein and has synergic effects with platelet-derived growth factor (PDGF) to enhance MK proliferation. Therefore, 5-HT is likely to be an important substance in the feedback regulation of thrombopoiesis.

  • An Alternative Growth Factor for Hematopoietic Stem Cells and Megakaryocytopoiesis.
    Blood, 2004
    Co-Authors: Mo Yang, Carmen Ka Yee Chuen, Ki Wai Chick, Nga Hin Pong, Tai Fai Fok
    Abstract:

    The role of serotonin (5-hydroxytryptamine, 5-HT) on the regulation of blood stem cell proliferation and thrombopoiesis has not been recognized until 1996, when we reported that serotonin has a mitogenic effect on murine Megakaryocytopoiesis via 5-HT2 receptors (Yang et al, Blood Coagul Fibrin 1996). Our study also indicated that the uptake ability of serotonin is well established in human megakaryoblasts (Yang et al, Int J Hematol, 1996). 5-HT 2A, 2B and 2C receptors were identified on human megakaryocytes and serotonin also promoted human Megakaryocytopoiesis via these receptors (Yang et al, Blood, 2001; 2002 suppl). Thus, we established a new concept that serotonin is a growth factor for Megakaryocytopoiesis (Yang et al, Blood, 2003 suppl). We further investigated the role of serotonin on human hematopoietic stem cells, bone marrow stromal cells and platelet formation. Serotonin (200 nM) significantly enhanced TPO, SCF plus FL -induced the ex vivo expansion of CD34+ cells, CD34+38- cells, CD41+61+ cells, CFU-GEMM and CFU-MK from cord blood CD34+ cells (MACS) (n=25) at day 8 (P

  • Effects of oxygen-induced lung damage on Megakaryocytopoiesis and platelet homeostasis in a rat model.
    Pediatric Research, 2003
    Co-Authors: Jie Yang, Mo Yang, Simon K M Lee, Janet S. K. Tam, Patrick Man Pan Yuen, Tai Fai Fok
    Abstract:

    Effects of Oxygen-Induced Lung Damage on Megakaryocytopoiesis and Platelet Homeostasis in a Rat Model

Beng H Chong - One of the best experts on this subject based on the ideXlab platform.

  • The Molecular Mechanisms of Serotonin in the Regulation of Megakaryocytopoiesis and TPO Production
    Blood, 2012
    Co-Authors: Mo Yang, Fanyi Meng, Bin Xiao, Beng H Chong
    Abstract:

    Abstract 3347 We have reported that serotonin (5-HT) show a promoting effect on cord blood CD34+ stem/progenitor cells (Yang et al, Stem Cells 2007). We also demonstrated that serotonin enhances murine megakaryopoiesis via 5-HT2 receptors (Yang et al. Blood Coagul Fibrinol 1996). In this present study, we explored how serotonin regulated human Megakaryocytopoiesis, proplatelet formation, and thrombopoietin (TPO) production. Our results indicated that serotonin significantly promoted human CFU-MK formation and reduced apoptosis in megakaryocytes through phosphorylation of Akt. These effects were attenuated by addition of ketanserin, a 5-HT2 receptor inhibitor. In addition, serotonin was able to stimulate the F-actin reorganization in megakaryocytes through activating the p-Erk1/2 expression. Bone marrow mesenchymal stromal cells (MSCs) are important in regulating Megakaryocytopoiesis through stimulating release of thrombopoietic growth factor, such as TPO. Our studies suggested that when activated by serotonin, bone marrow MSCs were induced to release significant amount of TPO by q-PCR, ELISA and cytokine-array assays. Our findings demonstrated an important role of serotonin played on Megakaryocytopoiesis. This effect was likely mediated via 5HT2 receptors with subsequent activation of Akt and Erk 1/2 phosphorylation, which led to survival of megakaryocytes and proplatelet formation. Serotonin also stimulated TPO released from MSCs, which indirectly promoted megakaryopoiesis. In present studies, we have demonstrated a positive “feed-back” control loop between MK-derived granule- serotonin and Megakaryocytopoiesis. These findings improved our knowledge on Megakaryocytopoiesis regulation and provided new clues on identifying novel thrombopoietic agents. It also deepened our understandings on how TPO production is regulated. Disclosures: No relevant conflicts of interest to declare.

  • Thrombospondin-1 inhibits in vitro Megakaryocytopoiesis via CD36
    Thrombosis Research, 2003
    Co-Authors: Mo Yang, Patrick Man Pan Yuen, Tai Fai Fok, Philip J. Hogg, Beng H Chong
    Abstract:

    Thrombospondin-1 (TSP-1) is an inhibitor of angiogenesis, inducing apoptosis of the endothelial cells via CD36 signaling mechanism. We investigated CD36 expression and the effect of TSP-1 on Megakaryocytopoiesis, with and without pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), and with and without blocking TSP-1 binding with receptor CD36 on megakaryocytic cells. Our data showed that TSP-1 induced a dose-dependent growth inhibition in both murine and human colony forming unit-megakaryocyte (CFU-MK) assays and significantly counteracted the mitogenic effect from PEG-rHuMGDF. Moreover, the growth suppression induced by TSP-1 was correlated with CD36 expression in megakaryocytic cell lines, where growth inhibition was demonstrated in CD36 positive (Meg-01, Dami and CHRF-288-11) but not in CD36 negative (M-07e) cell lines. More importantly, the inhibitory effect of TSP-1 on both human CFU-MK and Meg-01 cells was partially but significantly reversed by the addition of FA6-152 (anti-CD36), a blocking antibody which blocks the access of TSP-1 to CD36 receptor, suggesting that the TSP-1-induced inhibition of Megakaryocytopoiesis is probably mediated in part by the binding of TSP-1 to CD36 expressed on the megakaryocytic progenitors. Thus, our findings represent the first demonstration that TSP-1 inhibits in vitro Megakaryocytopoiesis via interaction with CD36.

  • Serotonin stimulates Megakaryocytopoiesis via the 5-ht2 receptor
    Blood Coagulation & Fibrinolysis, 1996
    Co-Authors: Yang M, Srikiatkhachorn A, Anthony M., Beng H Chong
    Abstract:

    It is known that platelet α-granule constituents including platelet-derived growth factor (PDGF), platelet factor 4 (PF4) and transforming growth factor-β (TGF-β) can affect Megakaryocytopoiesis. Serotonin, a platelet dense granule constituent has been shown to have a mitogenic effect on fibroblasts and smooth muscle cells but whether it has the same effect on megakaryocytes remains unclear. In this study, we investigated the effect of serotonin on Megakaryocytopoiesis and the possible mechanism of its effect using the mouse plasma clot culture method. The results show that (a) serotonin significantly stimulates megakaryocyte colony formation with maximum stimulation at 100 nM; (b) enhanced action is found between serotonin and interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin (EPO) and PDGF; (c) ketanserin, a 5-HT2 receptor antagonist, blocks the mitogenic effect of serotonin on Megakaryocytopoiesis; and (d) Meg-01 cells (a megakaryocyte cell line) express 5-HT2 receptors. This study demonstrates that serotonin has a mitogenic effect on Megakaryocytopoiesis and this effect may be mediated via the 5-HT2 receptor which is known to be coupled to G protein. It is suggested that serotonin may also be involved in the feedback control of Megakaryocytopoiesis.

  • Serotonin stimulates Megakaryocytopoiesis via the 5-HT2 receptor.
    Blood Coagulation & Fibrinolysis, 1996
    Co-Authors: Mo Yang, Srikiatkhachorn A, Anthony M., Beng H Chong
    Abstract:

    It is known that platelet alpha-granule constituents including platelet-derived growth factor (PDGF), platelet factor 4 (PF4) and transforming growth factor-beta (TGF-beta) can affect Megakaryocytopoiesis. Serotonin, a platelet dense granule constituent has been shown to have a mitogenic effect on fibroblasts and smooth muscle cells but whether it has the same effect on megakaryocytes remains unclear. In this study, we investigated the effect of serotonin on Megakaryocytopoiesis and the possible mechanism of its effect using the mouse plasma clot culture method. The results show that: (a) serotonin significantly stimulates megakaryocyte colony formation with maximum stimulation at 100 nM; (b) enhanced action is found between serotonin and interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin (EPO) and PDGF; (c) ketanserin, a 5-HT2 receptor antagonist, blocks the mitogenic effect of serotonin on Megakaryocytopoiesis; and (d) Meg-01 cells (a megakaryocyte cell line) express 5-HT2 receptors. This study demonstrates that serotonin has a mitogenic effect on Megakaryocytopoiesis and this effect may be mediated via the 5-HT2 receptor which is known to be coupled to G protein. It is suggested that serotonin may also be involved in the feedback control of Megakaryocytopoiesis.

Zhongchao Han - One of the best experts on this subject based on the ideXlab platform.

  • TPO-independent Megakaryocytopoiesis
    Critical Reviews in Oncology Hematology, 2008
    Co-Authors: Cui-ling Zheng, Renchi Yang, Zhongchao Han, Bin Zhou, Lu Liang
    Abstract:

    Abstract Megakaryocytopoiesis is a continuous developmental process of platelet production. In this process, a complex network of hemopoietic growth factors are involved, among which TPO (thrombopoietin) is the most thoroughly investigated regulator of MKs (megakaryocytes). In addition to TPO, other regulators also have non-negligible effects on Megakaryocytopoiesis. The majority of their effects are independent of TPO signaling. To date, TPO-independent Megakaryocytopoiesis forms a regulatory system that includes four signals and (an) unknown signaling pathway(s). These four pathways are the gp130 (glycoprotein 130)-dependent signaling pathway, the Notch pathway, NMDA (N-methyl- d -aspartate) receptor-mediated signaling, and the SDF-1 (stromal cell-derived factor-1)/FGF-4 (fibroblast growth factor-4) paradigm. Understanding of the TPO-independent regulatory system is important because the system may offer additional opportunities to understand the developmental process and the mechanisms of disorders characterized by abnormal MK and platelet production, such as thrombocytopenia and thrombocythemia, and to advance the development of therapeutics.

  • 2 Positive and negative regulation of Megakaryocytopoiesis
    Baillière's Clinical Haematology, 1997
    Co-Authors: Françoise Wendling, Zhongchao Han
    Abstract:

    The recently cloned physiological regulator of Megakaryocytopoiesis, known as Mpl ligand, thrombopoietin (TPO), megakaryocyte growth and development factor (MGDF) or megapoietin, is undergoing preclinical and clinical trials. This factor is an extremely potent thrombocytopoietic agent in vivo in normal animals, and accelerates platelet recovery in some but not all models of myelosuppression. Together with its apparent lack of adverse effects, the preclinical data suggest that TPO might permit the use of higher doses of chemotherapy in dose-intensive regimens and be useful in patients with ineffective platelet production or production abnormalities. The direct effects of TPO on primitive and various myeloid committed haematopoietic progenitor cells predict that TPO may be used in combination with other cytokines in a variety of clinical disorders. Along with the progress made in the understanding of the positive regulation of Megakaryocytopoiesis, accumulating data demonstrate that platelet production is also controlled by negative regulators with potential clinical applications. Some of these regulators are effective in the treatment of essential thrombocythaemia and myeloproliferative disorders, while others seem capable of protecting progenitor cells from the cytotoxicity of chemotherapeutic drugs.

  • Glycosaminoglycans enhance Megakaryocytopoiesis by modifying the activities of hematopoietic growth regulators.
    Journal of Cellular Physiology, 1996
    Co-Authors: Zhongchao Han, S. Bellucci, Z X Shen, J P Maffrand, Marc Pascal, Maurice Petitou, Jean-claude Lormeau, Jacques Caen
    Abstract:

    We have previously reported that heparin is capable of stimulating in vitro and in vivo Megakaryocytopoiesis in mice and has a thrombopoietic effect when given in chronic immune thrombocytopenic purpura and that heparin and several other glycosaminoglycans (GAGs) promote the growth of human megakaryoblastic cell lines in the presence of serum. We show here that GAGs, including heparan sulfate (HS), chondroitin sulfate (CS), dermantan sulfate (DS), and hyaluronic acid (HA), also stimulate in vitro growth of murine megakaryocyte progenitors and augment the diameter of individual megakaryocytes in the presence of serum. However, in a serum-free agar system, the GAGs alone had no effect on megakaryocyte colony formation, suggesting that GAGs cooperate with some serum factor(s) to exert their activity. We also show that heparin significantly potentiates the megakaryocytopoietic activity of C-Mpl ligand and interleukin (IL)-6 but not IL3, GM-CSF, SCF, and Epo. In addition, the GAGs significantly neutralize the inhibitory action of platelet factor 4 (PF4) and transforming growth factor β1 (TGFβ1) on megakaryocyte colony growth. These results demonstrate a stimulating activity of GAGs on Megakaryocytopoiesis by modifying the activity of several growth-regulating factors. © 1996 Wiley-Liss, Inc.

  • fraxiparin a low molecular weight heparin stimulates Megakaryocytopoiesis in vitro and in vivo in mice
    British Journal of Haematology, 1994
    Co-Authors: Z X Shen, J. P. Caen, N Basara, J P Maffrand, M Pascal, M Petitou, J C Lormeau, Zhongchao Han
    Abstract:

    Summary. The effect of a low-molecular-weight heparin, faxiparin (Nadroparinŕ;), on murine Megakaryocytopoiesis in vitro and in vivo was studied in comparison with unfractionated heparin. The addition of fraxiparin at 1–20 IU/ml into plasma clot cultures but not serum-free agar culture significantly enhanced MK colony growth. Furthermore, fraxiparin was found to potentiate the stimulating activity of aplastic anaemia serum (AAS) but not stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo), on MK colony growth in vitro, and to neutralize the inhibitory effect of platelet factor 4 (PF4) in vitro and in vivo. Fraxiparin also acted synergistically with heparin confactor II and antithrombin III to promote megakaryocyte colony formation. Intraperitoneal administration of fraxiparin twice daily for 4d at 0.1–25IU/injection increased in mice the level of blood platelet counts and the number of single MKs and CFU-MK in bone marrow. These data demonstrate that fraxiparin is able to positively regulate Megakaryocytopoiesis.

Andrew D. Leavitt - One of the best experts on this subject based on the ideXlab platform.

  • HEMATOPOIESIS A critical function for B-Raf at multiple stages of myelopoiesis
    2016
    Co-Authors: Tamihiro Kamata, Catrin A. Pritchard, Jing Kang, Tzong-hae Lee, Leszek Wojnowski, Andrew D. Leavitt
    Abstract:

    Raf kinases play an integral role in the classic mitogen-activated protein (MAP) kinase (Raf/MEK/extracellular signal-re-lated kinase [ERK]) intracellular signaling cascade, but their role in specific develop-mental processes is largely unknown. Using a genetic approach, we have identi-fied a role for B-Raf during hematopoietic progenitor cell development and during Megakaryocytopoiesis. Fetal liver and in vitro embryonic stem (ES) cell–derived myeloid progenitor development is quan-titatively impaired in the absence of B-Raf. Biochemical data suggest that this phenotype is due to the loss of a normally occurring rise in B-Raf expression and associated ERK1/2 activation during he-matopoietic progenitor cell formation. However, the presence of B-raf/ ES cell–derived myeloid progenitors in the bone marrow of adult chimeric mice indi-cates the lack of an obligate cell-autono-mous requirement for B-Raf in myeloid progenitor development. The lack of B-Raf also impairs Megakaryocytopoiesis. Thrombopoietin (Tpo)–induced in vitro expansion of ES cell–derived megakaryo-cyte-lineage cells fails to occur in the absence of B-Raf. Moreover, this quantita-tive in vitro defect in megakaryocyte-lineage expansion is mirrored by chimeric mice data that show reduced B-raf/ genotype contribution in megakaryocytes relative to its contribution in myeloid pro-genitors. Together, these data suggest that B-Raf plays a cell-autonomous role in Megakaryocytopoiesis and a permis-sive role in myeloid progenitor develop-ment. (Blood. 2005;106:833-840) © 2005 by The American Society of Hematolog

  • Raf-1 is not required for Megakaryocytopoiesis or TPO-induced ERK phosphorylation
    2016
    Co-Authors: Tamihiro Kamata, Andrew D. Leavitt, Catrin A. Pritchard, Thrombopoietin Stimulates Extracellular
    Abstract:

    signal-related kinase 1/2 (ERK1/2) phos-phorylation in megakaryocytes, and the classic mitogen-activated protein (MAP) kinase (Raf/mitogen-induced extracellu-lar kinase [MEK]/ERK) pathway has been implicated directly and indirectly to play a critical role in Megakaryocytopoiesis. How-ever, the involvement of specific Raf family members in Megakaryocytopoiesis is un-known. raf-1/ mice were therefore used to directly determine the role of Raf-1 in Megakaryocytopoiesis. Surprisingly, raf-1/ mice have a modestly higher platelet count than their raf-1/ littermates. None-theless, the absence of Raf-1 does not alter thrombopoietin-induced expansion of pri-mary megakaryocyte-lineage cells, the de-velopment of apoptotic megakaryocytes in the presence or absence of thrombopoi-etin, or the development of megakaryo-cyte DNA ploidy distribution. Moreover, raf-1/ megakaryocytes do not have a compensatory increase in A-Raf or B-Raf expression, and thrombopoietin-induced ERK1/2 phosphorylation is similar in raf-1/ and raf-1/ megakaryocytes. These unexpected findings demonstrate that Raf-1 is dispensable for megakaryocyto-poiesis, and for thrombopoietin-induced ERK1/2 activation in primary megakaryo-cyte-lineage cells. (Blood. 2004;103

  • Raf-1 is not required for Megakaryocytopoiesis or TPO-induced ERK phosphorylation.
    Blood, 2004
    Co-Authors: Tamihiro Kamata, Catrin Pritchard, Andrew D. Leavitt
    Abstract:

    Thrombopoietin stimulates extracellular signal-related kinase 1/2 (ERK1/2) phosphorylation in megakaryocytes, and the classic mitogen-activated protein (MAP) kinase (Raf/mitogen-induced extracellular kinase [MEK]/ERK) pathway has been implicated directly and indirectly to play a critical role in Megakaryocytopoiesis. However, the involvement of specific Raf family members in Megakaryocytopoiesis is unknown. raf-1-/- mice were therefore used to directly determine the role of Raf-1 in Megakaryocytopoiesis. Surprisingly, raf-1-/- mice have a modestly higher platelet count than their raf-1 + / + littermates. Nonetheless, the absence of Raf-1 does not alter thrombopoietin-induced expansion of primary megakaryocyte-lineage cells, the development of apoptotic megakaryocytes in the presence or absence of thrombopoietin, or the development of megakaryocyte DNA ploidy distribution. Moreover, raf-1-/- megakaryocytes do not have a compensatory increase in A-Raf or B-Raf expression, and thrombopoietin-induced ERK1/2 phosphorylation is similar in raf-1 - / - and raf-1 + / + megakaryocytes. These unexpected findings demonstrate that Raf-1 is dispensable for Megakaryocytopoiesis, and for thrombopoietin-induced ERK1/2 activation in primary megakaryocyte-lineage cells.

J. P. Caen - One of the best experts on this subject based on the ideXlab platform.

  • Studies of in vitro Megakaryocytopoiesis in adult immune thrombocytopenic purpura (ITP).
    European Journal of Haematology, 2009
    Co-Authors: S. Bellucci, Z. C. Han, J. P. Caen
    Abstract:

    In vitro Megakaryocytopoiesis was studied in 8 patients with chronic immune thrombocytopenia (ITP). A significant increase of megakaryocyte (MK) colony formation was observed in 5/5 patients studied. Furthermore, the serum of these 8 patients was able to enhance MK colony formation by normal marrow cells. This effect was neither due to a decrease of inhibitors of Megakaryocytopoiesis such as betathromboglobulin (beta TG) nor to the IgG fraction of patients' serum. In addition, the level of interleukin 6, which is above all a stimulus for MK maturation, was found within the normal range in 8/8 patients tested. These data suggest that in chronic ITP there is an increase of MK progenitor cell number which may be due to an increased level of MK colony-stimulating activity.

  • regulation of Megakaryocytopoiesis
    Pathophysiology of Haemostasis and Thrombosis, 1999
    Co-Authors: J. P. Caen, Z. C. Han, S. Bellucci, M Alemany
    Abstract:

    After 35 years of research, a physiological regulator of platelet production has been identified and the recombinant protein is available. With the discovery of thrombopoietin (TPO), its potential use

  • fraxiparin a low molecular weight heparin stimulates Megakaryocytopoiesis in vitro and in vivo in mice
    British Journal of Haematology, 1994
    Co-Authors: Z X Shen, J. P. Caen, N Basara, J P Maffrand, M Pascal, M Petitou, J C Lormeau, Zhongchao Han
    Abstract:

    Summary. The effect of a low-molecular-weight heparin, faxiparin (Nadroparinŕ;), on murine Megakaryocytopoiesis in vitro and in vivo was studied in comparison with unfractionated heparin. The addition of fraxiparin at 1–20 IU/ml into plasma clot cultures but not serum-free agar culture significantly enhanced MK colony growth. Furthermore, fraxiparin was found to potentiate the stimulating activity of aplastic anaemia serum (AAS) but not stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo), on MK colony growth in vitro, and to neutralize the inhibitory effect of platelet factor 4 (PF4) in vitro and in vivo. Fraxiparin also acted synergistically with heparin confactor II and antithrombin III to promote megakaryocyte colony formation. Intraperitoneal administration of fraxiparin twice daily for 4d at 0.1–25IU/injection increased in mice the level of blood platelet counts and the number of single MKs and CFU-MK in bone marrow. These data demonstrate that fraxiparin is able to positively regulate Megakaryocytopoiesis.

  • Regulation of human Megakaryocytopoiesis.
    Nouvelle revue francaise d'hematologie, 1990
    Co-Authors: Z. C. Han, S. Bellucci, J. P. Caen
    Abstract:

    Megakaryocytopoiesis is a complex, highly regulated cellular and biologic process which leads to the production of platelets. The proliferation of megakaryocyte (MK) progenitors is mainly regulated by interleukin-3, granulocyte-macrophage colony-stimulating factor and an as yet uncharacterized MK colony-stimulating factor. The maturation of MKs to produce platelets is essentially regulated by interleukin-6 and thrombopoietin. Optimal Megakaryocytopoiesis is controlled by appropriate combinations of positive and negative influence. Megakaryocytopoietic inhibition is controlled by transforming growth factor beta, platelet factor 4 and its related proteins, interferon-alpha and -gamma.