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Nature Immunology Jul 2010
Topics: Allergy and Immunology; Animals; Autoimmunity; Biomedical Research; Humans; Immunologic Memory; Lymphopoiesis; Periodicals as Topic
PubMed: 20562831
DOI: 10.1038/ni0710-545 -
Verhandlungen Der Anatomischen... 1963
Review
Topics: Bone Marrow; Hematopoiesis; Humans; Leukocytes; Leukocytosis; Leukopoiesis; Lymphocytes; Polycythemia Vera; Primary Myelofibrosis
PubMed: 14049238
DOI: No ID Found -
Bulletin of Experimental Biology and... Dec 2021We analyzed advantages of the liposomal form of Xymedon (50 and 100 mg/kg) over free Xymedon (in the corresponding doses) in leukopoiesis restoration in rats with...
Advantages of the Liposomal Form of Xymedon in Leukopoiesis Restoration against the Background of Myelosuppressive Therapy with Liposomal Antineoplastic Drugs in Experiment.
We analyzed advantages of the liposomal form of Xymedon (50 and 100 mg/kg) over free Xymedon (in the corresponding doses) in leukopoiesis restoration in rats with Walker-256 carcinoma treated with liposomal combination of doxorubicin (4 mg/kg) and cyclophosphamide (45 mg/kg) (single intravenous injection on day 11 after transplantation of tumor cells). Liposomal and free Xymedon were injected intravenously over 5 days starting from day 11 of the experiment. Changes in leukopoiesis in peripheral blood and myelograms were assessed on days 3 and 7 after chemotherapy. Liposomal Xymedon in both doses (unlike its free form) 2-fold increased the number of lymphocytes on day 3 after chemotherapy in comparison with the level observed after administration of liposomal cytostatics alone. Liposomal Xymedon in a dose of 50 mg/kg (but not 100 mg/kg) promoted the maintenance of monocyte count at the level of intact control on days 3 and 7 after chemotherapy. Liposomal Xymedon in a dose of 50 mg/kg and free Xymedon in a dose of 100 mg/kg equally stimulated the increase in myelocytes content in the bone marrow to the level of intact control on day 3 after chemotherapy, thus promoting restoration of granulocytopoiesis.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma 256, Walker; Cyclophosphamide; Dosage Forms; Doxorubicin; Female; Leukopoiesis; Liposomes; Myeloablative Agonists; Pyrimidines; Rats; Rats, Wistar
PubMed: 34855087
DOI: 10.1007/s10517-021-05362-6 -
Pharmacology & Therapeutics Jun 2019Granulocytes are the major type of phagocytes constituting the front line of innate immune defense against bacterial infection. In adults, granulocytes are derived from... (Review)
Review
Granulocytes are the major type of phagocytes constituting the front line of innate immune defense against bacterial infection. In adults, granulocytes are derived from hematopoietic stem cells in the bone marrow. Alcohol is the most frequently abused substance in human society. Excessive alcohol consumption injures hematopoietic tissue, impairing bone marrow production of granulocytes through disrupting homeostasis of granulopoiesis and the granulopoietic response. Because of the compromised immune defense function, alcohol abusers are susceptible to infectious diseases, particularly septic infection. Alcoholic patients with septic infection and granulocytopenia have an exceedingly high mortality rate. Treatment of serious infection in alcoholic patients with bone marrow inhibition continues to be a major challenge. Excessive alcohol consumption also causes diseases in other organ systems, particularly severe alcoholic hepatitis which is life threatening. Corticosteroids are the only therapeutic option for improving short-term survival in patients with severe alcoholic hepatitis. The existence of advanced alcoholic liver diseases and administration of corticosteroids make it more difficult to treat serious infection in alcoholic patients with the disorder of granulopoieis. This article reviews the recent development in understanding alcohol-induced disruption of marrow granulopoiesis and the granulopoietic response with the focus on progress in delineating cell signaling mechanisms underlying the alcohol-induced injury to hematopoietic tissue. Efforts in exploring effective therapy to improve patient care in this field will also be discussed.
Topics: Agranulocytosis; Alcoholism; Animals; Ethanol; Granulocytes; Hematopoietic Stem Cells; Homeostasis; Humans; Leukopoiesis
PubMed: 30831129
DOI: 10.1016/j.pharmthera.2019.03.001 -
Mitochondrial pyruvate metabolism and glutaminolysis toggle steady-state and emergency myelopoiesis.The Journal of Experimental Medicine Sep 2023To define the metabolic requirements of hematopoiesis, we examined blood lineages in mice conditionally deficient in genes required for long-chain fatty acid oxidation...
To define the metabolic requirements of hematopoiesis, we examined blood lineages in mice conditionally deficient in genes required for long-chain fatty acid oxidation (Cpt2), glutaminolysis (Gls), or mitochondrial pyruvate import (Mpc2). Genetic ablation of Cpt2 or Gls minimally impacted most blood lineages. In contrast, deletion of Mpc2 led to a sharp decline in mature myeloid cells and a slower reduction in T cells, whereas other hematopoietic lineages were unaffected. Yet MPC2-deficient monocytes and neutrophils rapidly recovered due to a transient and specific increase in myeloid progenitor proliferation. Competitive bone marrow chimera and stable isotope tracing experiments demonstrated that this proliferative burst was progenitor intrinsic and accompanied by a metabolic switch to glutaminolysis. Myeloid recovery after loss of MPC2 or cyclophosphamide treatment was delayed in the absence of GLS. Reciprocally, MPC2 was not required for myeloid recovery after cyclophosphamide treatment. Thus, mitochondrial pyruvate metabolism maintains myelopoiesis under steady-state conditions, while glutaminolysis in progenitors promotes emergency myelopoiesis.
Topics: Mice; Animals; Myelopoiesis; Hematopoiesis; Bone Marrow; Cyclophosphamide; Pyruvates
PubMed: 37249600
DOI: 10.1084/jem.20221373 -
Journal of Innate Immunity 2018An intact and fully functional innate immune system is critical in the defense against pathogens. Indeed, during systemic infection, the ability of the organism to cope... (Review)
Review
An intact and fully functional innate immune system is critical in the defense against pathogens. Indeed, during systemic infection, the ability of the organism to cope with the increased demand for phagocytes depends heavily on sufficient replenishment of mature myeloid cells. This process, designated emergency or demand-adapted myelopoiesis, requires the activation of hematopoietic progenitors in the bone marrow (BM), resulting in their proliferation and differentiation toward the myeloid lineage. Failure of BM progenitors to adapt to the enhanced need for mature cells in the periphery can be life-threatening, as indicated by the detrimental effect of chemotherapy-induced myelosuppression on the outcome of systemic infection. Recent advances demonstrate an important role of not only committed myeloid progenitors but also of hematopoietic stem cells (HSCs) in emergency myelopoiesis. In this regard, pathogen-derived products (e.g., Toll-like receptor ligands) activate HSC differentiation towards the myeloid lineage, either directly or indirectly, by inducing the production of inflammatory mediators (e.g., cytokines and growth factors) by hematopoietic and nonhematopoietic cell populations. The inflammatory mediators driving demand-adapted myelopoiesis target not only HSCs but also HSC-supportive cell populations, collectively known as the HSC niche, the microenvironment where HSCs reside. In this review, we discuss recent findings that have further elucidated the mechanisms that drive emergency myelopoiesis, focusing on the interactions of HSCs with their BM microenvironment.
Topics: Animals; Bone Marrow Cells; Cell Differentiation; Hematopoietic Stem Cells; Humans; Immunity, Innate; Myelopoiesis; Stem Cell Niche
PubMed: 29874678
DOI: 10.1159/000489406 -
Nature Immunology Dec 2023Aberrant differentiation of progenitor cells in the hematopoietic system is known to severely impact host immune responsiveness. Here we demonstrate that NOD1, a...
Aberrant differentiation of progenitor cells in the hematopoietic system is known to severely impact host immune responsiveness. Here we demonstrate that NOD1, a cytosolic innate sensor of bacterial peptidoglycan, also functions in murine hematopoietic cells as a major regulator of both the generation and differentiation of lymphoid progenitors as well as peripheral T lymphocyte homeostasis. We further show that NOD1 mediates these functions by facilitating STAT5 signaling downstream of hematopoietic cytokines. In steady-state, loss of NOD1 resulted in a modest but significant decrease in numbers of mature T, B and natural killer cells. During systemic protozoan infection this defect was markedly enhanced, leading to host mortality. Lack of functional NOD1 also impaired T cell-dependent anti-tumor immunity while preventing colitis. These findings reveal that, in addition to its classical role as a bacterial ligand receptor, NOD1 plays an important function in regulating adaptive immunity through interaction with a major host cytokine signaling pathway.
Topics: Animals; Mice; Colitis; Immunity, Innate; Ligands; Lymphopoiesis; Signal Transduction
PubMed: 37957354
DOI: 10.1038/s41590-023-01668-x -
Phytotherapy Research : PTR Feb 2019The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis...
The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis and leukopoiesis are interrelated, the effect of Silibinin on leukopoiesis of ES cells was investigated. Treatment of differentiating ES cells with hydrosoluble Silibinin-C-2',3-dihydrogen succinate dose-dependent increased the number of CD18 , CD45 , and CD68 cells, indicating leukocyte/macrophage differentiation. Silibinin treatment activated phosphoinositide 3-kinase (PI3K), AKT (protein kinase B), signal transducer and activator of transcription 3 (STAT3), stimulated hypoxia-induced factor-1α (HIF-1α), and vascular endothelial growth factor receptor 2 (VEGFR2) expression and raised intracellular nitric oxide (NO). Western blot experiments showed that upon coincubation with either the PI3K inhibitor LY294002, the STAT3 inhibitor Stattic, the AKT antagonist AKT inhibitor VIII, or the NO inhibitor L-NAME, the Silibinin-induced expression of CD18, CD45, and CD68 was abolished. Moreover, the stimulation of HIF-1α and VEGFR2 expression was blunted upon STAT3 and PI3K/AKT inhibition. Treatment of differentiating ES cells with L-NAME abolished the stimulation of VEGFR2 and VE-cadherin expression achieved with Silibinin, indicating that NO is involved in vasculogenesis and leukocyte differentiation pathways. In summary, the data of the present study demonstrate that Silibinin stimulates leukocyte differentiation of ES cells, which is associated to vasculogenesis and regulated by PI3K/AKT-, STAT3-, and NO-mediated signaling.
Topics: Animals; Chromones; Leukopoiesis; Mice; Silybum marianum; Morpholines; Mouse Embryonic Stem Cells; Nitric Oxide; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; STAT3 Transcription Factor; Signal Transduction; Silybin; Vascular Endothelial Growth Factor A
PubMed: 30548344
DOI: 10.1002/ptr.6241 -
Proceedings of the National Academy of... Oct 2021Trained immunity defines long-lasting adaptations of innate immunity based on transcriptional and epigenetic modifications of myeloid cells and their bone marrow...
Trained immunity defines long-lasting adaptations of innate immunity based on transcriptional and epigenetic modifications of myeloid cells and their bone marrow progenitors [M. Divangahi et al., 22, 2-6 (2021)]. Innate immune cells, however, do not exclusively differentiate between foreign and self but also react to host-derived molecules referred to as alarmins. Extracellular "labile" heme, released during infections, is a bona fide alarmin promoting myeloid cell activation [M. P. Soares, M. T. Bozza, 38, 94-100 (2016)]. Here, we report that labile heme is a previously unrecognized inducer of trained immunity that confers long-term regulation of lineage specification of hematopoietic stem cells and progenitor cells. In contrast to previous reports on trained immunity, essentially mediated by pathogen-associated molecular patterns, heme training depends on spleen tyrosine kinase signal transduction pathway acting upstream of c-Jun N-terminal kinases. Heme training promotes resistance to sepsis, is associated with the expansion of self-renewing hematopoetic stem cells primed toward myelopoiesis and to the occurrence of a specific myeloid cell population. This is potentially evoked by sustained activity of Nfix, Runx1, and Nfe2l2 and dissociation of the transcriptional repressor Bach2. Previously reported trained immunity inducers are, however, infrequently present in the host, whereas heme abundantly occurs during noninfectious and infectious disease. This difference might explain the vanishing protection exerted by heme training in sepsis over time with sustained long-term myeloid adaptations. Hence, we propose that trained immunity is an integral component of innate immunity with distinct functional differences on infectious disease outcome depending on its induction by pathogenic or endogenous molecules.
Topics: Animals; Epigenesis, Genetic; Heme; Humans; Immunity, Innate; Mice; Myelopoiesis
PubMed: 34663697
DOI: 10.1073/pnas.2102698118 -
Circulation Research Sep 2020
Topics: Atherosclerosis; Humans; Hyperglycemia; Myelopoiesis
PubMed: 32910740
DOI: 10.1161/CIRCRESAHA.120.317797