Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis.

Hepcidin, a key regulator of iron metabolism, decreases intestinal absorption of iron and its release from macrophages. Iron, anemia, hypoxia, and inflammation were reported to influence hepcidin expression. To investigate regulation of the expression of hepcidin and other iron-related genes, we manipulated erythropoietic activity in mice. Erythropoiesis was inhibited by irradiation or posttransfusion polycythemia and stimulated by phenylhydrazine administration and erythropoietin. Gene expression of hepcidin and other iron-related genes (hemojuvelin, DMT1, ferroportin, transferrin receptors, ferritin) in the liver was measured by the real-time polymerase chain reaction. Hepcidin expression increased despite severe anemia when hematopoiesis was inhibited by irradiation. Suppression of erythropoiesis by posttransfusion polycythemia or irradiation also increased hepcidin mRNA levels. Compensated hemolysis induced by repeated phenylhydrazine administration did not change hepcidin expression. The decrease caused by exogenous erythropoeitin was blocked by postirradiation bone marrow suppression. The hemolysis and anemia decrease hepcidin expression only when erythropoiesis is functional; on the other hand, if erythropoiesis is blocked, even severe anemia does not lead to a decrease of hepcidin expression, which is indeed increased. We propose that hepcidin is exclusively sensitive to iron utilization for erythropoiesis and hepatocyte iron balance, and these changes are not sensed by other genes involved in the control of iron metabolism in the liver.

Estimation of extent of cell death in different stages of normal murine hematopoiesis.

Murine hematopoiesis has been analyzed by many authors, and available data allow for quantitative evaluation of this dynamic process. In this study, the capacity of several populations of the bone marrow clonogenic cells (progenitors) to produce blood cells was compared with their actual production. The cell cycle progression rate was directly measured in the following types of hematopoietic progenitors: day 8 colony-forming units-spleen, GM-colony-forming cells, BFU-E, and CFU-E in normal mice. The cell cycle progression rates of the individual progenitors, together with their numbers in the whole hematopoietic tissue, were used to calculate the absolute numbers produced daily in each population. The data reviewed from literature were analyzed in parallel. The capacity of the progenitors to produce mature blood cells were derived from the daily production of progenitors multiplied by their clonogenic potential. This theoretical capacity to produce blood cells was compared to the actual blood cell production determined from the turnover of circulating blood elements. The comparison strongly suggested an intensive cell death rate occurring at the early stages of differentiation and its decline as the hematopoietic cells become more differentiated and mature.

Granulocytic progenitor cells (CFU-C) in canine blood: mobilization by dexamethasone?

DXM application in dogs in an amount of 0.3 or 0.6 mg/kg b.w. results in a very transient increase of CFU-C within 1 h after administration and a subsequent progressive decrease of circulating CFU-C reaching a nadir at about 7 h. The pattern seen in the blood CFU-C concentration matches the pattern of change seen in the total lymphocyte population. The CFU-C changes observed do not correspond to the change of the PMN numbers in the peripheral blood after DXM. There is a 3 fold increase in the number of circulating PMNs. The data suggest that the blood CFU-C follow in principle the pattern of the other mononuclear cells, usually described as "lymphocytes". The pattern of change of CFU-C and lymphocytes however must not be interpreted to mean that the pathophysiological mechanisms behind this changes are the same considering the CFU-C population and the other lymphocyte populations.

Transplantation of bone marrow cells with changed haemoglobin type.

Haemoglobin was used as a marker for the detection of radiation chimera in rats. After a single blood loss, the synthesis of haemoglobin type had changed, as observed in peripheral blood one week after bleeding. After one month the haemoglobin pattern was the same in the experimental rats and in the control animals. Twenty-four hours before bone marrow transplantation the donors were bled. Haemoglobin synthesis had changed also in the recipients. In contrast with a single blood loss, this change of haemoglobin type persisted as observed one year after transplantation. The cells with changed synthesis can repeatedly be retransplanted.

Bone marrow cell separation on Ficoll gradient.

Cell fraction from rat and murine bone marrow were obtained by sedimentation at unit gravity. A linear gradient of polymerized sucrose (Ficoll) was used and some properties of individual cell fractions were studied. The 3rd cell fraction containing the lymphoblasts and lymphocytes contained also stem cells.

Haemoglobin types in peripheral blood and bone marrow cells in rats after a single blood loss.

The authors studied quantitative changes in the synthesis of haemoglobin types in rat peripheral erythrocytes and in the cells of the bone marrow erythrocytic series after a single blood loss. They demonstrated that raised synthesis of given haemoglobin types could be found in the peripheral cells 5-7 days after blood loss. These changes could already be detected in the bone marrow cells 24 hours after blood loss. The question of the probable site and level of the origin of altered haemoglobin synthesis is discussed.