Fraser, Stuart T and Midwinter, Robyn G and Coupland, Lucy A and Kong, Stephanie and Berger, Birgit S and Yeo, Jia Hao and Andrade, Osvaldo Cooley and Cromer, Deborah and Suarna, Cacang and Lam, Magdalena and Maghzal, Ghassan J and Chong, Beng H and Parish, Christopher R and Stocker, Roland (2015) Heme oxygenase-1 deficiency alters erythroblastic island formation, steady-state erythropoiesis and red blood cell lifespan in mice. Haematologica, 100 (5). pp.601-10. ISSN 1592-8721 (DOAJ OA)
Preview |
Text
Fraser 2015 HOx1 _Haematologica OA.pdf Download (2MB) | Preview |
Abstract
Heme oxygenase-1 is critical for iron recycling during red blood cell turnover, whereas its impact on steady-state erythropoiesis and red blood cell lifespan is not known. We show here that in 8- to 14-week old mice, heme oxygenase-1 deficiency adversely affects steady-state erythropoiesis in the bone marrow. This is manifested by a decrease in Ter-119(+)-erythroid cells, abnormal adhesion molecule expression on macrophages and erythroid cells, and a greatly diminished ability to form erythroblastic islands. Compared with wild-type animals, red blood cell size and hemoglobin content are decreased, while the number of circulating red blood cells is increased in heme oxygenase-1 deficient mice, overall leading to microcytic anemia. Heme oxygenase-1 deficiency increases oxidative stress in circulating red blood cells and greatly decreases the frequency of macrophages expressing the phosphatidylserine receptor Tim4 in bone marrow, spleen and liver. Heme oxygenase-1 deficiency increases spleen weight and Ter119(+)-erythroid cells in the spleen, although α4β1-integrin expression by these cells and splenic macrophages positive for vascular cell adhesion molecule 1 are both decreased. Red blood cell lifespan is prolonged in heme oxygenase-1 deficient mice compared with wild-type mice. Our findings suggest that while macrophages and relevant receptors required for red blood cell formation and removal are substantially depleted in heme oxygenase-1 deficient mice, the extent of anemia in these mice may be ameliorated by the prolonged lifespan of their oxidatively stressed erythrocytes.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 04 Feb 2016 00:20 |
| Last Modified: | 03 Nov 2016 04:48 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/311 |
Actions (login required)
 |
View Item |