Carbon Monoxide Induced Erythroid Differentiation of K562 Cells Mimics the Central Macrophage Milieu in Erythroblastic Islands
Figure 9
Schematic presentation of CO production and function in the erythroblastic island.
Shaded Red - Hb at varying concentrations; Blue – nucleus; Green – CO. Stages of differentiation in EI erythroblasts are shown in a clockwise fashion. 1: Clearance of FLVCR-associated “free” heme by hemopexin. 2: HO-1 induction by FLVCR associated “free” heme. 3: Enucleation of terminally differentiated erythroblast in EI. 3a: Engulfment of nucleus containing Hb remnants. 3b: Reticulocyte movement toward blood circulation. 4: HO-1 induction by Hb heme remnants. 4a. Dispersion of Hb in central macrophage. 4b. Formation of “free” heme from Hb phagocytosed with nucleus. 4c: Induction of HO-1 by “free” heme. (The membrane attached HO-1 is shown in the macrophage center for illustration purpose only.) 5: CO production by HO-1, leading to terminal differentiation. 5a. CO dispersion reaching erythroblast. 5b. Nuclear condensation and peripheral shift. 5c. Accelerated Hb synthesis, followed by membrane-associated “free” heme. 5d. Terminal erythroid differentiation upon attaining maximal Hb content.