Ilana Amoyal1, Eitan Fibach. 1. Department of Hematology, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Abstract
BACKGROUND: Hemoglobin (Hb) production switches upon birth from fetal Hb (HbF) to adult Hbs. HbF production is reactivated in sickle cell anemia and beta-thalassemia, where increased HbF ameliorates clinical symptoms and HbF-stimulating drugs are used for treatment. Understanding of the switch is therefore of basic interest and important for rational drug design. We studied the switch by determining changes after birth in the frequency and HbF-content of HbF-containing red blood cells (F-RBC) and reticulocytes (F-retics). METHODS: Blood samples of neonatal cord, babies in their first year and adults were stained with both phycoerythrin-conjugated anti-human HbF antibodies and the nucleic acid dye thiazol-orange, and analyzed by flow-cytometry. RBC and retics were distinguished by their different thiazol orange-derived fluorescence and their HbF content was determined by the intensity of phycoerythrin-derived fluorescence. RESULTS: The frequency of both F-RBC and F-retics decreases with time after birth. In most cases, the percentage of F-RBC was higher, but their HbF-content was lower than that of retics. The HbF content of the F-RBC and the F-retics showed a gradual decrease with age. CONCLUSIONS: The results can be explained by two models: (A) A pool of homogenous stem cells that undergo gradual changes in their globin transcription pattern. (B) A pool of heterogeneous stem cells with varying HbF potentials that become active in an age-dependent manner: first, cells with a high HbF potential and then cells with a gradually lower HbF potential. In both models, these changes are induced by a biological clock and environmental factors.
BACKGROUND: Hemoglobin (Hb) production switches upon birth from fetal Hb (HbF) to adult Hbs. HbF production is reactivated in sickle cell anemia and beta-thalassemia, where increased HbF ameliorates clinical symptoms and HbF-stimulating drugs are used for treatment. Understanding of the switch is therefore of basic interest and important for rational drug design. We studied the switch by determining changes after birth in the frequency and HbF-content of HbF-containing red blood cells (F-RBC) and reticulocytes (F-retics). METHODS: Blood samples of neonatal cord, babies in their first year and adults were stained with both phycoerythrin-conjugated anti-human HbF antibodies and the nucleic acid dye thiazol-orange, and analyzed by flow-cytometry. RBC and retics were distinguished by their different thiazol orange-derived fluorescence and their HbF content was determined by the intensity of phycoerythrin-derived fluorescence. RESULTS: The frequency of both F-RBC and F-retics decreases with time after birth. In most cases, the percentage of F-RBC was higher, but their HbF-content was lower than that of retics. The HbF content of the F-RBC and the F-retics showed a gradual decrease with age. CONCLUSIONS: The results can be explained by two models: (A) A pool of homogenous stem cells that undergo gradual changes in their globin transcription pattern. (B) A pool of heterogeneous stem cells with varying HbF potentials that become active in an age-dependent manner: first, cells with a high HbF potential and then cells with a gradually lower HbF potential. In both models, these changes are induced by a biological clock and environmental factors.
Authors: Carolina A Braghini; Flavia C Costa; Halyna Fedosyuk; Renee Y Neades; Lesya V Novikova; Matthew P Parker; Robert D Winefield; Kenneth R Peterson Journal: Exp Biol Med (Maywood) Date: 2016-03-04