Limits...
Heme oxygenase-1 deletion affects stress erythropoiesis.

Cao YA, Kusy S, Luong R, Wong RJ, Stevenson DK, Contag CH - PLoS ONE (2011)

Bottom Line: Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.In the spleens of mice that received hmox(+/-) cells, we show (i) decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii) increases in the insoluble iron levels and decreases in the soluble iron levels; (iii) increased numbers of Mac-1(+)-cells expressing TNF-α; and (iv) decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America.

ABSTRACT

Background: Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1) deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.

Methodology/principal findings: We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/-) or hmox(+/+) bone marrow cells, we evaluated (i) the erythrocyte parameters in the peripheral blood; (ii) the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii) the patterns of histological iron staining; and (iv) the number of Mac-1(+)-cells expressing TNF-α. In the spleens of mice that received hmox(+/-) cells, we show (i) decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii) increases in the insoluble iron levels and decreases in the soluble iron levels; (iii) increased numbers of Mac-1(+)-cells expressing TNF-α; and (iv) decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.

Conclusions/significance: As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

Show MeSH

Related in: MedlinePlus

HO-1 haploinsufficiency disrupts erythrocyte parameters in the peripheral blood.Lethally irradiated mice were transplanted with 2×107 hmox+/+ or hmox+/− BM cells. Peripheral blood was drawn at each given time-point post-engraftment and was analyzed for the reticulocyte count (A), hematocrit percentage (B), RBC count (C), and hemoglobin level (D). The ratios of the RBC counts, hematocrit percentages, and hemoglobin levels of the hmox+/− to hmox+/+ genotypes are plotted in (E) using the same data shown in (B-D). The mean ± SEM is shown for five mice per genotype; *P≤0.05, **P≤0.01.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3105104&req=5

pone-0020634-g001: HO-1 haploinsufficiency disrupts erythrocyte parameters in the peripheral blood.Lethally irradiated mice were transplanted with 2×107 hmox+/+ or hmox+/− BM cells. Peripheral blood was drawn at each given time-point post-engraftment and was analyzed for the reticulocyte count (A), hematocrit percentage (B), RBC count (C), and hemoglobin level (D). The ratios of the RBC counts, hematocrit percentages, and hemoglobin levels of the hmox+/− to hmox+/+ genotypes are plotted in (E) using the same data shown in (B-D). The mean ± SEM is shown for five mice per genotype; *P≤0.05, **P≤0.01.

Mentions: Eight days after engraftment, the reticulocyte counts increased rapidly in recipients of hmox+/− BM cells, reaching a level of ∼250% of those in the recipients of hmox+/+ BM cells (1.22±0.48×105 per uL versus 0.47±0.14×105 per uL; n = 5, *P = 0.031) (Figure 1A). In contrast, 15 days after engraftment, the reticulocyte counts in recipients of hmox+/− BM cells were only 27% of those observed in the mice that received hmox+/+ BM cells (4.22±1.35×105 per uL versus 15.38±3.75×105 per uL; n = 5, **P = 0.007) (Figure 1A). This is consistent with our previous report in which we demonstrate accelerated hematopoiesis that was not sustainable after transplant [14].


Heme oxygenase-1 deletion affects stress erythropoiesis.

Cao YA, Kusy S, Luong R, Wong RJ, Stevenson DK, Contag CH - PLoS ONE (2011)

HO-1 haploinsufficiency disrupts erythrocyte parameters in the peripheral blood.Lethally irradiated mice were transplanted with 2×107 hmox+/+ or hmox+/− BM cells. Peripheral blood was drawn at each given time-point post-engraftment and was analyzed for the reticulocyte count (A), hematocrit percentage (B), RBC count (C), and hemoglobin level (D). The ratios of the RBC counts, hematocrit percentages, and hemoglobin levels of the hmox+/− to hmox+/+ genotypes are plotted in (E) using the same data shown in (B-D). The mean ± SEM is shown for five mice per genotype; *P≤0.05, **P≤0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105104&req=5

pone-0020634-g001: HO-1 haploinsufficiency disrupts erythrocyte parameters in the peripheral blood.Lethally irradiated mice were transplanted with 2×107 hmox+/+ or hmox+/− BM cells. Peripheral blood was drawn at each given time-point post-engraftment and was analyzed for the reticulocyte count (A), hematocrit percentage (B), RBC count (C), and hemoglobin level (D). The ratios of the RBC counts, hematocrit percentages, and hemoglobin levels of the hmox+/− to hmox+/+ genotypes are plotted in (E) using the same data shown in (B-D). The mean ± SEM is shown for five mice per genotype; *P≤0.05, **P≤0.01.
Mentions: Eight days after engraftment, the reticulocyte counts increased rapidly in recipients of hmox+/− BM cells, reaching a level of ∼250% of those in the recipients of hmox+/+ BM cells (1.22±0.48×105 per uL versus 0.47±0.14×105 per uL; n = 5, *P = 0.031) (Figure 1A). In contrast, 15 days after engraftment, the reticulocyte counts in recipients of hmox+/− BM cells were only 27% of those observed in the mice that received hmox+/+ BM cells (4.22±1.35×105 per uL versus 15.38±3.75×105 per uL; n = 5, **P = 0.007) (Figure 1A). This is consistent with our previous report in which we demonstrate accelerated hematopoiesis that was not sustainable after transplant [14].

Bottom Line: Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.In the spleens of mice that received hmox(+/-) cells, we show (i) decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii) increases in the insoluble iron levels and decreases in the soluble iron levels; (iii) increased numbers of Mac-1(+)-cells expressing TNF-α; and (iv) decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America.

ABSTRACT

Background: Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1) deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.

Methodology/principal findings: We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/-) or hmox(+/+) bone marrow cells, we evaluated (i) the erythrocyte parameters in the peripheral blood; (ii) the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii) the patterns of histological iron staining; and (iv) the number of Mac-1(+)-cells expressing TNF-α. In the spleens of mice that received hmox(+/-) cells, we show (i) decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii) increases in the insoluble iron levels and decreases in the soluble iron levels; (iii) increased numbers of Mac-1(+)-cells expressing TNF-α; and (iv) decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.

Conclusions/significance: As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

Show MeSH
Related in: MedlinePlus