Heme oxygenase-1 deletion affects stress erythropoiesis.
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 prog...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3105104?pdf=render |
| _version_ | 1818572841453355008 |
|---|---|
| author | Yu-An Cao Sophie Kusy Richard Luong Ronald J Wong David K Stevenson Christopher H Contag |
| author_facet | Yu-An Cao Sophie Kusy Richard Luong Ronald J Wong David K Stevenson Christopher H Contag |
| author_sort | Yu-An Cao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-15T00:03:02Z |
| format | Article |
| id | doaj.art-0832df4be20b4251b53e34bf6e52fdc8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-15T00:03:02Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0832df4be20b4251b53e34bf6e52fdc82022-12-21T22:42:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e2063410.1371/journal.pone.0020634Heme oxygenase-1 deletion affects stress erythropoiesis.Yu-An CaoSophie KusyRichard LuongRonald J WongDavid K StevensonChristopher H ContagBACKGROUND: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.http://europepmc.org/articles/PMC3105104?pdf=render |
| spellingShingle | Yu-An Cao Sophie Kusy Richard Luong Ronald J Wong David K Stevenson Christopher H Contag Heme oxygenase-1 deletion affects stress erythropoiesis. PLoS ONE |
| title | Heme oxygenase-1 deletion affects stress erythropoiesis. |
| title_full | Heme oxygenase-1 deletion affects stress erythropoiesis. |
| title_fullStr | Heme oxygenase-1 deletion affects stress erythropoiesis. |
| title_full_unstemmed | Heme oxygenase-1 deletion affects stress erythropoiesis. |
| title_short | Heme oxygenase-1 deletion affects stress erythropoiesis. |
| title_sort | heme oxygenase 1 deletion affects stress erythropoiesis |
| url | http://europepmc.org/articles/PMC3105104?pdf=render |
| work_keys_str_mv | AT yuancao hemeoxygenase1deletionaffectsstresserythropoiesis AT sophiekusy hemeoxygenase1deletionaffectsstresserythropoiesis AT richardluong hemeoxygenase1deletionaffectsstresserythropoiesis AT ronaldjwong hemeoxygenase1deletionaffectsstresserythropoiesis AT davidkstevenson hemeoxygenase1deletionaffectsstresserythropoiesis AT christopherhcontag hemeoxygenase1deletionaffectsstresserythropoiesis |