title: Heme oxygenase-1 deletion affects stress erythropoiesis.
abstract: BACKGROUND
  Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1) deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.
  
  
  RESULTS
  We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/-) or hmox(+/+) bone marrow cells, we evaluated (i) the erythrocyte parameters in the peripheral blood; (ii) the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii) the patterns of histological iron staining; and (iv) the number of Mac-1(+)-cells expressing TNF-α. In the spleens of mice that received hmox(+/-) cells, we show (i) decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii) increases in the insoluble iron levels and decreases in the soluble iron levels; (iii) increased numbers of Mac-1(+)-cells expressing TNF-α; and (iv) decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.
  
  
  CONCLUSIONS
  As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Cao
authors.forename: Sophie
authors.initials: S
authors.lastname: Kusy
authors.forename: Richard
authors.initials: R
authors.lastname: Luong
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wong
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000235:genetics*; D007501:Iron; D051379:Mice; D018345:Mice, Knockout; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology*
chemical_list: D007501:Iron; D051547:Heme Oxygenase-1