carbon monoxide induced erythroid differentiation of k562 cells mimics the central macrophage milieu in erythroblastic islands一氧化碳红细胞分化诱导的k562细胞模拟中央巨噬细胞环境erythroblastic岛屿.pdfVIP

Carbon Monoxide Induced Erythroid Differentiation of K562 Cells Mimics the Central Macrophage Milieu in Erythroblastic Islands 1 2. 1 . Shlomi Toobiak , Mati Shaklai , Nurith Shaklai * 1 Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 2 Department of Hematology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract Growing evidence supports the role of erythroblastic islands (EI) as microenvironmental niches within bone marrow (BM), where cell-cell attachments are suggested as crucial for erythroid maturation. The inducible form of the enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in erythroblasts where hemoglobin (Hb) is synthesized. Yet, the central macrophage, which retains high HO-1 activity, might be suitable to take over degradation of extra, harmful, Hb heme. Of these enzymatic products, only the hydrophobic gas molecule - CO can transfer from the macrophage to surrounding erythroblasts directly via their tightly attached membranes in the terminal differentiation stage. Based on the above, the study hypothesized CO to have a role in erythroid maturation. Thus, the effect of CO gas as a potential erythroid differentiation inducer on the common model for erythroid progenitors, K562 cells, was explored. Cells were kept under oxygen lacking environment to mimic BM conditions. Nitrogen anaerobic atmosphere (N2A) served as control for CO atmosphere (COA). Under both atmospheres cells proliferation ceased: in N2A due to cell death, while in COA as a result of erythroid differentiation. Maturation was evaluated by increased glycophorin A expression and Hb concentration. Addition