heme oxygenase-1 deletion affects stress erythropoiesis血红素oxygenase-1删除影响红细胞生成压力.pdfVIP

Heme Oxygenase-1 Deletion Affects Stress Erythropoiesis 1 1 2 1 1 Yu-An Cao , Sophie Kusy , Richard Luong , Ronald J. Wong , David K. Stevenson , Christopher H. Contag1* 1 Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America, 2 Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California, United States of America 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. Methodology/Principal Findings: We used a transplant model to induce stress conditions. In irradiated recipients that received hmox+/ 2 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-a. In the spleens of mice that received hmox+/ 2 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; (