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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)601-610
Number of pages10
JournalHaematologica
Volume100
Issue number5
DOIs
Publication statusPublished - 2015
Externally publishedYes

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