Adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5’-N-methyluronamide (IB-MECA) has been tested from the point of view of potentiating the effects of hematopoietic growth factors interleukin-3 (IL-3), stem cell factor (SCF), granulocyte- macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) on the growth of hematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) in suspension of normal mouse bone marrow cells in vitro. IB-MECA alone induced no GM-CFC growth. Significant elevation of numbers of GM-CFC evoked by the combinations of IB-MECA with IL-3, SCF, or GM-CSF as compared with these growth factors alone has been noted. Combinat ion of IB-MECA with G-CSF did not induce significantly higher numbers of GM-CFC in comparison with G-CSF alone. Joint action of three drugs, namely of IB-MECA + IL-3 + GM-CSF, produced significantly higher numbers of GM-CFC in comparison with the combinations of IB-MECA + IL-3, IB-MECA + GM-CSF, or IL-3 + GM-CSF. These results give evidence of a significant role of selective activation of adenosine A3 receptors in stimulation of the growth of granulocyte/macrophage hematopoietic progenitor cells., M. Hofer ... [et al.]., and Obsahuje seznam literatury
Four mouse bone marrow or thymus cell populations, namely granulopoietic/monocytopoietic, erythropoietic, B-lymphopoietic, and T-lymphopoietic precursor cells have been assayed by RTPCR technique for the presence and relative amounts of adenosine A1, A2a, A2b, and A3 receptor mRNA. It has been found that (i) all four populations studied express all four adenosine receptor subtypes, (ii) the A1 receptor is the least expressed in all populations studied, (iii) the A3 receptor is markedly expressed in the populations of granulopoietic/monocytopoietic and erythropoietic cells, (iv) the A2a receptor is markedly expressed in the populations of B-lymphopoietic and T-lymphopoietic cells, and v) the A2b receptor does not predominate in any of the precursor cells studied. Our data offer a new possibility for the assessment of the readiness of these cells to respond, by receptor-mediated mechanisms, to adenosine or its analogs present in the tissues as a result of endogenous processes and/or following their administration., D. Štreitová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Several members of the TGF-ß family are known to effectively regulate the fate of hematopoietic progenitor cells in a complex and context-dependent manner. Growth differentiation factor-15 (GDF15) is a divergent member of the TGF-ß family. This stress-induced cytokine has been proposed to possess immunomodulatory functions and its high expression is often associated with progression of a variety of pathological conditions. GDF15 is also induced by chemotherapy and irradiation. Very few fundamental studies have been published regarding the effect of GDF15 in hematopoiesis. In this study, we analyzed the hematological status of untreated and γ-irradiated mice deficient for GDF15 as a result of genetic knock-out (KO), in order to clarify the regulatory role of GDF15 in hematopoiesis. Significant differences between GDF15 KO mice and their pertinent WT controls were found in the parameters of blood monocyte numbers, blood platelet size, and distribution width, as well as in the values of bone marrow granulocyte/macrophage progenitor cells. Different tendencies of some hematological parameters in the GDF15 KO mice in normal conditions and those under exposure of the mice to ionizing radiation were registered. These findings are discussed in the context of the GDF15 gene function and its lack under conditions of radiation-induced damage., M. Hofer, Z. Hoferová, J. Remšík, M. Nováková, J. Procházková, R. Fedr, J. Kohoutek, L. Dušek, A. Hampl, K. Souček., and Obsahuje bibliografii
We investigated hematopoiesis in untreated and ionizing radiation-exposed cyclooxygenase-2-deficient (COX-2 KO) mice. We performed a complex hematological analysis of 16 parameters in untreated COX-2 KO male mice or COX-2 KO male mice irradiated with the dose of 4 Gy of γ-rays and their wildtype littermates. At baseline, hematopoiesis was increased in COX-2-deficient mice, but attenuated by irradation in COX-2- deficient mice compared to wildtype. To conclude, the antiinflammatory action of the COX-2 genetic disruption plays a positive role in hematopoiesis under basal conditions but is detrimental following radiation exposure., M. Hofer, Z. Hoferová L. Dušek, K. Souček, A. Gruzdev., and Obsahuje bibliografii
The purpose of the study was to describe and compare normal and 5-fluorouracil (5-FU)-suppressed hematopoiesis in adenosine A3 receptor knock-out (A3AR KO) mice and their wild-type (WT) counterparts. To meet the purpose, a complex hematological analysis comprising nineteen peripheral blood and bone marrow parameters was performed in the mice. Defects previously observed in the peripheral blood erythrocyte and thrombocyte parameters of the A3AR KO mice were confirmed. Compartments of the bone marrow progenitor cells for granulocytes/ macrophages and erythrocytes were enhanced in the control, as well as in the 5-FU-administered A3AR KO mice. 5-FU-induced hematopoietic suppression, evaluated on day 2 after the administration of the cytotoxic drug, was found to be significantly deeper in the A3AR KO mice compared with their WT counterparts, as measured at the level of the bone marrow progenitor cells. The rate of regeneration, as assessed between days 2 and 7 after 5-FU administration, was observed in the population of the granulocyte/macrophage progenitor cells to be higher in the A3AR KO mice in comparison with the WT ones. The increased depth of 5-FU-induced suppression in the compartments of the hematopoietic progenitor cells in the A3AR KO mice represents probably a hitherto undescribed further consequence of the lack of adenosine A3 receptors and indicates its synergism with the pharmacologically induced cytotoxic action of 5-FU., M. Hofer, M. Pospíšil, L. Dušek, Z. Hoferová, D. Komůrková., and Obsahuje bibliografii
Hematopoiesis-modulating action of meloxicam, a cyclooxygenase-2 inhibitor, has been evaluated in mice. Increased serum level of granulocyte colony-stimulating factor (G-CSF) after meloxicam administration has been found in sublethally γ-irradiated animals. In further experiments hematopoiesis-stimulating effects of meloxicam and G-CSF given alone or in combination have been investigated. Granulocyte/macrophage progenitor cells counts were used to monitor these effects. Meloxicam and exogenous G-CSF did not act synergistically when given in combination, but could be mutually substituted during their repeated administration. The results suggest a promising possibility of using meloxicam as an auxiliary drug reducing the high costs of G-CSF therapy of myelosuppression., M. Hofer, M. Pospíšil, V. Znojil, J. Holá, A. Vacek, D. Štreitová., and Obsahuje bibliografii a bibliografické odkazy
Recent results of the authors have demonstrated that the elevation of extracellular adenosine induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), a soluble adenosine prodrug, mediates radioprotective effects in mice. Furthermore, it has been shown that this action is induced by at least two mechanisms: (1) protection by hypoxia as a result of the effects of treatment on the cardiovascular system (bradycardia, vasodilation), and (2) an enhanced regeneration of the radiation-perturbed hematopoiesis. Here, it was ascertained that the joint use of an optimal dose of noradrenaline given with dipyridamole and AMP combination eliminates the hypothermic and hypoxic effects of the treatment, but preserves the radioprotective action of dipyridamole and AMP combination in terms of hematopoietic recovery and partially also survival enhancing effects of the drugs in gamma-irradiated mice. These findings might be of importance for attempts to obtain available and tolerable radioprotective pharmacological prescriptions for clinical use.
The effect of antigenic bacterial lysate IRS-19 on the recovery of blood cells was studied in mice injured by a single dose of 7 Gy irradiation. The preirradiation administration of IRS-19 accelerated the recovery of leukocytes, reticulocytes and platelets in peripheral blood. The recovery of leukocytes 9-14 days after irradiation in protected animals was accompanied by a higher level of band forms of granulocytes as well as activated lymphoid and monocytoid cells., N.O. Macková, P. Fedoročko., and Obsahuje bibliografii
Leptin is a 16 kDa protein hormone involved in food intake, energy expenditure regulation and numerous other physiological processes. Recently, leptin has been demonstrated to stimulate hematopoietic stem cells in vitro. The aim of our study was to measure serum leptin and erythropoietin levels in patients with sideropenic (n =18) and pernicious anemia (n=7) before and during anemia treatment. Blood samples for the blood count, leptin and erythropoietin determinations were obtained by venepunction at the time of the diagnosis of anemia and after partial and complete anemia recovery. The relationships of serum leptin levels to erythropoietin levels and blood count parameters were also studied. No significant differences in serum leptin levels between the groups studied were found. The serum leptin levels in none of groups were modified by treatment of anemia (basal levels, the levels during treatment and after anemia recovery were 13.1±14.5 vs 12.8±15.6 vs 12.0±14.8 ng/ml in patients with sideropenic anemia and 7.8±8.5 vs 9.5±10.0 vs 8.9±6.6 ng/ml in patients with pernicious anemia). The erythropoietin levels were higher at the time of anemia in both groups and decreased significantly after partial or complete recovery. Serum leptin levels in both groups correlated positively with the body mass index. No significant relationships were found between serum leptin levels and erythropoietin values or various parameters of the peripheral blood count. We conclude that serum leptin levels in patients with sideropenic and pernicious anemia positively correlate with the body mass index but are not influenced by the treatment of anemia., M. Marková, M. Haluzík, J. Svobodová, M. Rosická, J. Nedvídková, T. Haas., and Obsahuje bibliografii