title: Heme oxygenase-1 deficiency alters erythroblastic island formation, steady-state erythropoiesis and red blood cell lifespan in mice.
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.
authors: Laboratory for Blood Cell Development, School of Medical Sciences (Physiology, Anatomy & Histology), Sydney Medical School, The University of Sydney, Australia.
authors: Stuart T
authors: ST
authors: Fraser
authors: Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, The University of Sydney, Australia.
authors: Robyn G
authors: RG
authors: Midwinter
authors: The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors: Lucy A
authors: LA
authors: Coupland
authors: Vascular Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, Australia.
authors: Stephanie
authors: S
authors: Kong
authors: Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, The University of Sydney, Australia.
authors: Birgit S
authors: BS
authors: Berger
authors: Laboratory for Blood Cell Development, School of Medical Sciences (Physiology, Anatomy & Histology), Sydney Medical School, The University of Sydney, Australia.
authors: Jia Hao
authors: JH
authors: Yeo
authors: Laboratory for Blood Cell Development, School of Medical Sciences (Physiology, Anatomy & Histology), Sydney Medical School, The University of Sydney, Australia.
authors: Osvaldo Cooley
authors: OC
authors: Andrade
authors: Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia.
authors: Deborah
authors: D
authors: Cromer
authors: Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, The University of Sydney, Australia Vascular Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, Australia.
authors: Cacang
authors: C
authors: Suarna
authors: Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, The University of Sydney, Australia Vascular Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, Australia.
authors: Magda
authors: M
authors: Lam
authors: Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, The University of Sydney, Australia Vascular Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, Australia School of Medical Sciences, Faculty of Medicine, University of New South Wales, Kensington.
authors: Ghassan J
authors: GJ
authors: Maghzal
authors: Department of Medicine, St George Clinical School, University of New South Wales, Kogarah, Australia.
authors: Beng H
authors: BH
authors: Chong
authors: The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors: Christopher R
authors: CR
authors: Parish
authors: Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, The University of Sydney, Australia Vascular Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, Australia School of Medical Sciences, Faculty of Medicine, University of New South Wales, Kensington r.stocker@victorchang.edu.au.
authors: Roland
authors: R
authors: Stocker
mesh_terms: D000743:Anemia, Hemolytic; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics*; D006130:Growth Disorders; D051547:Heme Oxygenase-1 / Q000172:deficiency*; D016130:Immunophenotyping; D019189:Iron Metabolism Disorders; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D013154:Spleen / Q000166:cytology
chemical_list: D051547:Heme Oxygenase-1