Zinc metabolism and metallothionein expression in bone marrow during erythropoiesis

1993 ◽  
Vol 264 (5) ◽  
pp. E770-E775 ◽  
Author(s):  
K. L. Huber ◽  
R. J. Cousins

Zinc metabolism and metallothionein induction in rat bone marrow were investigated during induced erythropoiesis. Redistribution of body zinc was measured with 65Zn after acute blood loss in rats fed zinc-restricted or zinc-adequate diets. Uptake of 65Zn by bone marrow was related to time after blood loss, metallothionein induction, and dietary zinc status. Increased 65Zn uptake by marrow of zinc-restricted rats suggests a minimal amount of zinc is necessary to support expansion of the erythrocytic compartment. Zinc induction of marrow metallothionein also occurred in rats in which anemia was produced using phenylhydrazine. Anemic rats which were administered zinc had higher concentrations of marrow metallothionein compared with control rats. Induction of marrow metallothionein by zinc in nonanemic rats required prior treatment with erythropoietin. Percoll fractionation showed marrow metallothionein was most abundant in erythroblasts. These experiments suggest metallothionein synthesis occurs in erythropoietin-sensitive precursor cells in the marrow in response to increased zinc accessibility.

1993 ◽  
Vol 104 (4) ◽  
pp. 1039-1048
Author(s):  
Z. Prakapas ◽  
M. Denoyelle ◽  
C. Dargemont ◽  
F.G. Kroese ◽  
J.P. Thiery ◽  
...  

The bone marrow precursor cells seeding the thymus have been difficult to investigate using fresh bone marrow and in vivo thymus reconstitution assays. We have therefore designed a short-term bone marrow culture system allowing the study of thymus-repopulating cells in the marrow microenvironment. Low-density rat bone marrow cells were grown on pre-established mouse bone marrow stromal cell layers. Cocultured cells were maintained either under steroid-free conditions (Whitlock/Witte-type culture) or in the presence of 10(−7) M hydrocortisone (Dexter-type culture). After 3 days in vitro, the unanchored cell fractions were tested for their ability to colonize and repopulate fetal mouse thymic lobes in vitro. Both fresh low-density cells and Whitlock/Witte-type cultures, but not Dexter-type cultures, gave rise intrathymically to significant numbers of rat donor-type Thy-1.1high CD2+ CD5low CD43+ cells accounting for 50% to 90% of the organ-cultured cells at day 14. Repopulation of fetal mouse thymic lobes by rat Thy-1.1high cells could be used as a readout assay for initiation of thymopoiesis from bone marrow precursor cells, since 90% of the cells were CD3-/low and TCR alpha beta-/low and 15% of the cells co-expressed CD4 and CD8. Dose-response analysis showed that thymus repopulating cells were at least maintained, if not amplified during the 3-day culture period, leading to at least a 10-fold enrichment as compared to unfractionated bone marrow. Unlike fresh low-density cells before culture, short-term Whitlock/Witte-type cultures were depleted in myeloid-restricted precursor cells. In culture, the thymus-repopulating activity was predominantly associated with a 10% lymphoid cell subset which did not express the B-lineage-associated antigens revealed by HIS24 (the rat B220 equivalent) and HIS50 mAbs. We propose that unanchored thymus-repopulating cells enriched in Whitlock/Witte-type cultures may represent lymphoid-restricted, T-cell precursors of the bone marrow capable of emigrating and colonizing the thymus.


2018 ◽  
Vol 314 (1) ◽  
pp. F132-F139 ◽  
Author(s):  
Seham Rabadi ◽  
Ikemesit Udo ◽  
David E. Leaf ◽  
Sushrut S. Waikar ◽  
Marta Christov

Fibroblast growth factor 23 (FGF23) production is upregulated by iron deficiency and hypoxia. However, the influence of acute blood loss, and the resulting increases in circulating erythropoietin, on FGF23 production is unknown. Using wild-type C57BL/6 mice, we show that acute loss of 10% total blood volume leads to an increase in plasma C-terminal FGF23 (cFGF23) levels within 6 h, while plasma levels of intact FGF23, phosphate, calcium, parathyroid hormone, iron, and ferritin remain similar to control mice without acute blood loss. Volume resuscitation with PBS did not significantly alter these findings. The increase in plasma cFGF23 levels in bled animals was accompanied by increased plasma erythropoietin levels at 6 h. Administration of erythropoietin led to an acute increase in plasma cFGF23 levels similar to that observed in acute blood loss. Fgf23 mRNA expression was increased 20-fold in bone marrow, but not in bone, of bled vs. control mice, suggesting bone marrow as a key source of elevated plasma FGF23 levels following acute blood loss. To extend these findings to humans, we measured plasma cFGF23 levels in 131 critically ill patients admitted to the intensive care unit. In univariate and multivariate models, we found a positive association between number of red blood cell transfusions, an indirect indicator of acute blood loss, and plasma cFGF23 levels. We conclude that FGF23 production is rapidly increased after acute blood loss and that erythropoietin may be the mediator of this increase. Thus erythropoietin may represent a novel physiological regulator of FGF23 production.


Tsitologiya ◽  
2018 ◽  
Vol 60 (2) ◽  
pp. 89-95 ◽  
Author(s):  
A. V. Deryugina ◽  
◽  
G. A. Boyarinov ◽  
I. S. Simutis ◽  
V. O. Nikolskiy ◽  
...  
Keyword(s):  

Author(s):  
M. Sharavina

The first successful blood transfusions were aimed at saving lives of patients with acute blood loss, application of donated blood is much wider today. Expansion of informational work with donors, including development of understanding in a donor concerning importance of the donor program in patient’s life, as well as creation of the Blood Service, which is responsible for promotion, collection of blood and its components, their storage and transportation, contributes to the development of regular and ongoing donation. The author reviewed the regulatory framework for blood donation.


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