Heme oxygenase-1 deficiency alters erythroblastic Island formation, steady-state erythropoiesis and red blood cell lifespan in mice
dc.contributor.author | Fraser, Stuart T | en_AU |
dc.contributor.author | Midwinter, Robyn G | en_AU |
dc.contributor.author | Coupland, Lucy | en_AU |
dc.contributor.author | Kong, Stephanie | en_AU |
dc.contributor.author | Berger, Birgit S. | en_AU |
dc.contributor.author | Yeo, Jia Hao | en_AU |
dc.contributor.author | Andrade, Osvaldo Cooley | en_AU |
dc.contributor.author | Cromer, Deborah | en_AU |
dc.contributor.author | Suarna, Cacang | en_AU |
dc.contributor.author | Lam, Magda | en_AU |
dc.contributor.author | Maghzal, Ghassan J. | en_AU |
dc.contributor.author | Chong, Beng | en_AU |
dc.contributor.author | Stocker, Roland | en_AU |
dc.contributor.author | Parish, Christopher | en_AU |
dc.date.accessioned | 2015-12-10T23:35:22Z | |
dc.date.issued | 2015 | |
dc.date.updated | 2015-12-10T11:41:01Z | |
dc.description.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. | |
dc.identifier.issn | 0390-6078 | |
dc.identifier.uri | http://hdl.handle.net/1885/69832 | |
dc.publisher | Ferrata Storti Foundation | |
dc.rights | Author/s retain copyright | en_AU |
dc.source | Haematologica | |
dc.title | Heme oxygenase-1 deficiency alters erythroblastic Island formation, steady-state erythropoiesis and red blood cell lifespan in mice | |
dc.type | Journal article | |
dcterms.accessRights | Open Access | en_AU |
local.bibliographicCitation.issue | 5 | |
local.bibliographicCitation.lastpage | 610 | |
local.bibliographicCitation.startpage | 601 | |
local.contributor.affiliation | Fraser, Stuart T, Sydney Medical School, University of Sydney | |
local.contributor.affiliation | Midwinter, Robyn G, Sydney Medical school, University of Sydney | |
local.contributor.affiliation | Coupland, Lucy, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Kong, Stephanie, The Victor Chang Cardiac Research Institute | |
local.contributor.affiliation | Berger, Birgit S., School of Medical Sciences, University of Sydney | |
local.contributor.affiliation | Yeo, Jia Hao, Sydney Medical School, University of Sydney | |
local.contributor.affiliation | Andrade, Osvaldo Cooley, Sydney Medical School, University of Sydney | |
local.contributor.affiliation | Cromer, Deborah, University of New South Wales | |
local.contributor.affiliation | Suarna, Cacang, School of Medical Sciences, University of Sydney | |
local.contributor.affiliation | Lam, Magda, School of Medical Sciences, University of Sydney | |
local.contributor.affiliation | Maghzal, Ghassan J., University of Sydney | |
local.contributor.affiliation | Chong, Beng, University of New South Wales | |
local.contributor.affiliation | Parish, Christopher, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Stocker, Roland, University of Sydney | |
local.contributor.authoremail | u3562509@anu.edu.au | |
local.contributor.authoruid | Coupland, Lucy, u3562509 | |
local.contributor.authoruid | Parish, Christopher, u6900322 | |
local.description.notes | Imported from ARIES | |
local.identifier.absfor | 111601 - Cell Physiology | |
local.identifier.absseo | 920108 - Immune System and Allergy | |
local.identifier.ariespublication | a383154xPUB2135 | |
local.identifier.citationvolume | 100 | |
local.identifier.doi | 10.3324/haematol.2014.116368 | |
local.identifier.scopusID | 2-s2.0-84929147920 | |
local.identifier.uidSubmittedBy | a383154 | |
local.type.status | Published Version |
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