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Heme oxygenase-1 deficiency alters erythroblastic Island formation, steady-state erythropoiesis and red blood cell lifespan in mice

Fraser, Stuart T; Midwinter, Robyn G; Coupland, Lucy; Kong, Stephanie; Berger, Birgit S.; Yeo, Jia Hao; Andrade, Osvaldo Cooley; Cromer, Deborah; Suarna, Cacang; Lam, Magda; Maghzal, Ghassan J.; Chong, Beng; Stocker, Roland; Parish, Christopher

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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...[Show more]

dc.contributor.authorFraser, Stuart T
dc.contributor.authorMidwinter, Robyn G
dc.contributor.authorCoupland, Lucy
dc.contributor.authorKong, Stephanie
dc.contributor.authorBerger, Birgit S.
dc.contributor.authorYeo, Jia Hao
dc.contributor.authorAndrade, Osvaldo Cooley
dc.contributor.authorCromer, Deborah
dc.contributor.authorSuarna, Cacang
dc.contributor.authorLam, Magda
dc.contributor.authorMaghzal, Ghassan J.
dc.contributor.authorChong, Beng
dc.contributor.authorStocker, Roland
dc.contributor.authorParish, Christopher
dc.date.accessioned2015-12-10T23:35:22Z
dc.identifier.issn0390-6078
dc.identifier.urihttp://hdl.handle.net/1885/69832
dc.description.abstractHeme 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.publisherFerrata Storti Foundation
dc.rightsAuthor/s retain copyright
dc.sourceHaematologica
dc.titleHeme oxygenase-1 deficiency alters erythroblastic Island formation, steady-state erythropoiesis and red blood cell lifespan in mice
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume100
dc.date.issued2015
local.identifier.absfor111601 - Cell Physiology
local.identifier.ariespublicationa383154xPUB2135
local.type.statusPublished Version
local.contributor.affiliationFraser, Stuart T, Sydney Medical School, University of Sydney
local.contributor.affiliationMidwinter, Robyn G, Sydney Medical school, University of Sydney
local.contributor.affiliationCoupland, Lucy, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKong, Stephanie, The Victor Chang Cardiac Research Institute
local.contributor.affiliationBerger, Birgit S., School of Medical Sciences, University of Sydney
local.contributor.affiliationYeo, Jia Hao, Sydney Medical School, University of Sydney
local.contributor.affiliationAndrade, Osvaldo Cooley, Sydney Medical School, University of Sydney
local.contributor.affiliationCromer, Deborah, University of New South Wales
local.contributor.affiliationSuarna, Cacang, School of Medical Sciences, University of Sydney
local.contributor.affiliationLam, Magda, School of Medical Sciences, University of Sydney
local.contributor.affiliationMaghzal, Ghassan J., University of Sydney
local.contributor.affiliationChong, Beng, University of New South Wales
local.contributor.affiliationParish, Christopher, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationStocker, Roland, University of Sydney
local.bibliographicCitation.issue5
local.bibliographicCitation.startpage601
local.bibliographicCitation.lastpage610
local.identifier.doi10.3324/haematol.2014.116368
local.identifier.absseo920108 - Immune System and Allergy
dc.date.updated2015-12-10T11:41:01Z
local.identifier.scopusID2-s2.0-84929147920
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

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