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Physiological Reviews Oct 2002P2X receptors are membrane ion channels that open in response to the binding of extracellular ATP. Seven genes in vertebrates encode P2X receptor subunits, which are... (Review)
Review
P2X receptors are membrane ion channels that open in response to the binding of extracellular ATP. Seven genes in vertebrates encode P2X receptor subunits, which are 40-50% identical in amino acid sequence. Each subunit has two transmembrane domains, separated by an extracellular domain (approximately 280 amino acids). Channels form as multimers of several subunits. Homomeric P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 channels and heteromeric P2X2/3 and P2X1/5 channels have been most fully characterized following heterologous expression. Some agonists (e.g., alphabeta-methylene ATP) and antagonists [e.g., 2',3'-O-(2,4,6-trinitrophenyl)-ATP] are strongly selective for receptors containing P2X1 and P2X3 subunits. All P2X receptors are permeable to small monovalent cations; some have significant calcium or anion permeability. In many cells, activation of homomeric P2X7 receptors induces a permeability increase to larger organic cations including some fluorescent dyes and also signals to the cytoskeleton; these changes probably involve additional interacting proteins. P2X receptors are abundantly distributed, and functional responses are seen in neurons, glia, epithelia, endothelia, bone, muscle, and hemopoietic tissues. The molecular composition of native receptors is becoming understood, and some cells express more than one type of P2X receptor. On smooth muscles, P2X receptors respond to ATP released from sympathetic motor nerves (e.g., in ejaculation). On sensory nerves, they are involved in the initiation of afferent signals in several viscera (e.g., bladder, intestine) and play a key role in sensing tissue-damaging and inflammatory stimuli. Paracrine roles for ATP signaling through P2X receptors are likely in neurohypophysis, ducted glands, airway epithelia, kidney, bone, and hemopoietic tissues. In the last case, P2X7 receptor activation stimulates cytokine release by engaging intracellular signaling pathways.
Topics: Adenosine Triphosphate; Animals; Cloning, Molecular; Epithelial Cells; Hematopoietic System; Humans; Ion Channels; Muscles; Neurons; Receptors, Purinergic P2; Tissue Distribution
PubMed: 12270951
DOI: 10.1152/physrev.00015.2002 -
Nature Oct 2019Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains...
Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.
Topics: Blood Cells; Cellular Microenvironment; Female; Fetus; Flow Cytometry; Gene Expression Profiling; Hematopoiesis; Humans; Liver; Lymphoid Tissue; Single-Cell Analysis; Stem Cells
PubMed: 31597962
DOI: 10.1038/s41586-019-1652-y -
American Journal of Transplantation :... Sep 2013Osteoimmunology is a field of research dedicated to the study of the interactions between the immune system, the hemopoietic system and bone. Among the cells of the... (Review)
Review
Osteoimmunology is a field of research dedicated to the study of the interactions between the immune system, the hemopoietic system and bone. Among the cells of the immune system that regulate bone cells and the hemopoietic function are T lymphocytes. These cells secrete inflammatory cytokines that promote bone resorption, as well as Wnt ligands that stimulate bone formation. In addition, T cells regulate bone homeostasis by cross talking with BM stromal cells and osteoblastic cells via CD40 ligand (CD40L) and other costimulatory molecules. This article describes the immune cells relevant to bone and the hemopoietic function, reviews the role of lymphocytes as mediators of the effects of PTH and estrogen in bone and the hemopoietic system and discusses the implication of osteoimmunology for transplant medicine.
Topics: Animals; B-Lymphocytes; Bone Marrow Transplantation; Bone Resorption; Bone Transplantation; Bone and Bones; CD40 Ligand; Estrogens; Hematopoiesis; Humans; Lymphocyte Activation; Mice; Osteogenesis; Osteoporosis; Osteoprotegerin; Ovariectomy; Parathyroid Hormone; T-Lymphocytes
PubMed: 23915249
DOI: 10.1111/ajt.12380 -
The Journal of Pathology Jul 2022The dynamical process of cell division that underpins homeostasis in the human body cannot be directly observed in vivo, but instead is measurable from the pattern of... (Review)
Review
The dynamical process of cell division that underpins homeostasis in the human body cannot be directly observed in vivo, but instead is measurable from the pattern of somatic genetic or epigenetic mutations that accrue in tissues over an individual's lifetime. Because somatic mutations are heritable, they serve as natural lineage tracing markers that delineate clonal expansions. Mathematical analysis of the distribution of somatic clone sizes gives a quantitative readout of the rates of cell birth, death, and replacement. In this review we explore the broad range of somatic mutation types that have been used for lineage tracing in human tissues, introduce the mathematical concepts used to infer dynamical information from these clone size data, and discuss the insights of this lineage tracing approach for our understanding of homeostasis and cancer development. We use the human colon as a particularly instructive exemplar tissue. There is a rich history of human somatic cell dynamics surreptitiously written into the cell genomes that is being uncovered by advances in sequencing and careful mathematical analysis lineage of tracing data. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Cell Lineage; Colon; Humans; Mutation; Neoplasms; United Kingdom
PubMed: 35415852
DOI: 10.1002/path.5911 -
Pathobiology : Journal of... 2011Erythropoietin (EPO), the main hemopoietic hormone synthesized by the kidney as well as by the liver in fetal life, is implicated in mammalian erythropoiesis. Production... (Review)
Review
Erythropoietin (EPO), the main hemopoietic hormone synthesized by the kidney as well as by the liver in fetal life, is implicated in mammalian erythropoiesis. Production and secretion of EPO and the expression of its receptor (EPO-R) are regulated by tissue oxygenation. EPO and EPO-R, expressed in several tissues, exert pleiotropic activities and have different effects on nonhemopoietic cells. EPO is a cytokine with antiapoptotic activity and plays a potential neuroprotective and cardioprotective role against ischemia. EPO is also involved in angiogenesis, neurogenesis, and the immune response. EPO can prevent metabolic alterations, neuronal and vascular degeneration, and inflammatory cell activation. Consequently, EPO may be of therapeutic use for a variety of disorders. Many tumors express EPO and/or EPO-R, but the action of EPO on tumor cells remains controversial. It has been suggested that EPO promotes the proliferation and survival of cancer cells expressing EPO-R. On the other hand, other reports have concluded that EPO-R plays no role in tumor progression. This review provides a detailed insight into the nonhemopoietic role of EPO and its mechanism(s) of action which may lead to a better understanding of its potential therapeutic value in diverse clinical settings.
Topics: Animals; Antineoplastic Agents; Erythropoiesis; Erythropoietin; Humans; Kidney; Neoplasms; Neovascularization, Pathologic; Receptors, Erythropoietin
PubMed: 21474975
DOI: 10.1159/000322975 -
Asian Journal of Andrology Mar 2012Androgen deprivation therapy (ADT) has been associated with a plethora of adverse effects, consistent with the androgen dependency of multiple reproductive and somatic... (Review)
Review
Androgen deprivation therapy (ADT) has been associated with a plethora of adverse effects, consistent with the androgen dependency of multiple reproductive and somatic tissues. One such tissue is the hemopoietic system, and one of the most predictable consequences of ADT is the development of anemia. Although anemia caused by ADT is rarely severe, ADT is often given to frail, elderly men with increased susceptibility to anemia due to multiple other causes. ADT-associated anemia may contribute to fatigue and reduced quality of life (QoL) in such men, although this requires further study. While anemia is an independent risk factor of mortality in men with prostate cancer, it is not known whether treatment of ADT-associated anemia alters clinically important outcomes, or whether treatment affects mortality. Awareness of the phenomenon of ADT-induced anemia should avoid unnecessary work-up in mild cases of normocytic normochromic anemia. However, assessment and treatment of more severe anemia may be required. This should be determined on an individual basis. In contrast to the well-described actions of ADT on erythropoiesis, its effect on other hemopoietic lineages has been less well elucidated. While preclinical studies have found roles for androgens in maturation and differentiated function of neutrophils, lymphocytes and platelets, the implications of these findings for men with prostate cancer receiving ADT require further studies.
Topics: Androgen Antagonists; Anemia; Erythropoiesis; Hematopoiesis; Humans; Incidence; Male; Prostatic Neoplasms
PubMed: 22231300
DOI: 10.1038/aja.2011.102 -
Cellular & Molecular Immunology Apr 2004The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived cells.... (Review)
Review
The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived cells. Although the common functions of DCs are antigen-processing and T-lymphocyte activation, they differ in surface markers, migratory patterns, and cytokine output. These differences can determine the fate of the T cells they activate. Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively. The original concept that all DCs were of myeloid origin was questioned by several recent studies, which demonstrated that in addition to the DCs derived from myeloid precursors, some DCs could also be efficiently generated from lymphoid-restricted precursors. Moreover, it has been shown recently that both conventional DCs and pDCs can be generated by the Flt3 expressing hemopoietic progenitors regardless of their myeloid- or lymphoid-origin. These findings suggest an early developmental flexibility of precursors for DCs and pDCs. This review summarizes some recent observations on the development of DC system in both human and mouse.
Topics: Animals; Antigens, CD; Cell Differentiation; Dendritic Cells; Hematopoietic Stem Cells; Humans; Lymphoid Tissue; Phenotype
PubMed: 16212897
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Dec 2023Acquired aplastic anemia (AA) is a bone marrow failure (BMF) disease, characterized by fatty bone marrow (BM) and BM hypocellularity resulted from auto-immune...
Acquired aplastic anemia (AA) is a bone marrow failure (BMF) disease, characterized by fatty bone marrow (BM) and BM hypocellularity resulted from auto-immune dysregulated T cells-mediated destruction of BM haemopoietic stem cells (HPSC). The objective of this study was to investigate potential therapeutic effect of irisin, a molecule involved in adipose tissue transition, on AA mouse model. Our results showed that the concentration of irisin in serum was lower in AA patients than in healthy controls, suggesting a role of irisin in the pathogenesis of AA. In the AA mice, irisin administration prolonged the survival rate, prevented or attenuated peripheral pancytopenia, and preserved HPSC in the BM. Moreover, irisin also markedly reduced BM adipogenesis. In vitro results showed that irisin increased both cell proliferation and colony numbers of HPSC. Furthermore, our results demonstrated that irisin upregulated the expression of mitochondrial ATPase Inhibitory Factor 1 (IF1) in HPSC, inhibited the activation of mitochondrial fission protein (DRP1) and enhanced aerobic glycolysis. Taken together, our findings indicate novel roles of irisin in the pathogenesis of AA, and in the protection of HPSC through stimulation of proliferation and regulation of mitochondria function, which provides a proof-of-concept for the application of irisin in AA therapy.
Topics: Animals; Humans; Mice; Anemia, Aplastic; Bone Marrow; Bone Marrow Cells; Fibronectins; Pancytopenia; Hematopoietic Stem Cells
PubMed: 37952356
DOI: 10.1016/j.biopha.2023.115863 -
Experimental Hematology Nov 2021It has recently emerged that tissue-resident macrophages are key regulators of several stem cell niches orchestrating tissue formation during development, as well as... (Review)
Review
It has recently emerged that tissue-resident macrophages are key regulators of several stem cell niches orchestrating tissue formation during development, as well as postnatally, when they also organize the repair and regeneration of many tissues including the hemopoietic tissue. The fact that macrophages are also master regulators and effectors of innate immunity and inflammation allows them to coordinate hematopoietic response to infections, injuries, and inflammation. After recently reviewing the roles of phagocytes and macrophages in regulating normal and pathologic hematopoietic stem cell niches, we now focus on the key roles of macrophages in regulating erythropoiesis and iron homeostasis. We review herein the recent advances in understanding how macrophages at the center of erythroblastic islands form an erythropoietic niche that controls the terminal differentiation and maturation of erythroblasts into reticulocytes; how red pulp macrophages in the spleen control iron recycling and homeostasis; how these macrophages coordinate emergency erythropoiesis in response to blood loss, infections, and inflammation; and how persistent infections or inflammation can lead to anemia of inflammation via macrophages. Finally, we discuss the technical challenges associated with the molecular characterization of erythroid island macrophages and red pulp macrophages.
Topics: Anemia; Animals; Erythroblasts; Erythropoiesis; Humans; Inflammation; Iron; Macrophages; Persistent Infection; Stem Cell Niche
PubMed: 34500024
DOI: 10.1016/j.exphem.2021.08.011 -
Journal of Applied Physiology... Jul 2010The effects of endurance or maximal exercise on mobilization of bone marrow-derived hemopoietic and angiogenetic progenitors in healthy subjects are poorly defined. In...
The effects of endurance or maximal exercise on mobilization of bone marrow-derived hemopoietic and angiogenetic progenitors in healthy subjects are poorly defined. In 10 healthy amateur runners, we collected venous blood before, at the end of, and the day after a marathon race (n = 9), and before and at the end of a 1.5-km field test (n = 8), and measured hemopoietic and angiogenetic progenitors by flow cytometry and culture assays, as well as plasma or serum concentrations of several cytokines/growth factors. After the marathon, CD34(+) cells were unchanged, whereas clonogenetic assays showed decreased number of colonies for both erythropoietic (BFU-E) and granulocyte-monocyte (CFU-GM) series, returning to baseline the morning post-race. Conversely, CD34(+) cells, BFU-E, and CFU-GM increased after the field test. Angiogenetic progenitors, assessed as CD34(+)KDR(+) and CD133(+)VE-cadherin(+) cells or as adherent cells in culture expressing endothelial markers, increased after both endurance and maximal exercise but showed a different pattern between protocols. Interleukin-6 increased more after the marathon than after the field test, whereas hepatocyte growth factor and stem cell factor increased similarly in both protocols. Plasma levels of angiopoietin (Ang) 1 and 2 increased after both types of exercise, whereas the Ang-1-to-Ang-2 ratio or vascular endothelial growth factor-A were little affected. These data suggest that circulating hemopoietic progenitors may be utilized in peripheral tissues during prolonged endurance exercise. Endothelial progenitor mobilization after exercise in healthy trained subjects appears modulated by the type of exercise. Exercise-induced increase in growth factors suggests a physiological trophic effect of exercise on the bone marrow.
Topics: AC133 Antigen; Adult; Angiogenesis Inducing Agents; Antigens, CD; Antigens, CD34; Athletes; Cadherins; Cytokines; Endothelial Cells; Erythroid Precursor Cells; Glycoproteins; Granulocytes; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; Humans; Male; Middle Aged; Neovascularization, Physiologic; Peptides; Physical Endurance; Running
PubMed: 20448032
DOI: 10.1152/japplphysiol.01344.2009