Preferential hemolysis of immature erythrocytes in experimental iron deficiency anemia: source of erythropoietic bilirubin formation.
Bilirubin-(14)C production was measured in rats transfused with labeled erythrocytes from animals with iron deficiency anemia, a condition associated with ineffective erythropoiesis. With labeled reticulocytes harvested 1 day after the administration of glycine-2-(14)C, conversion of hemoglobin-(14)C to bilirubin averaged 47.3% over the 3 days of observation; the corresponding value for reticulocytes from normal rats was only 1.7%. Findings were not altered by splenectomy. Bilirubin-(14)C production fell to 35.8% with iron-deficient cells harvested 3 days after glycine-(14)C administration, and declined further to a plateau averaging 25% with cells labeled 5, 7, 10, or 15 days earlier. The latter values still far exceed those for mature erythrocytes from normal animals.The findings indicate that experimental iron deficiency anemia is associated with hemolysis of red cells of various ages, but with preferential destruction of the youngest cells. Degradation of hemoglobin from reticulocytes is sufficient to account for a major fraction of the increase in erythropoietic bilirubin production found in this disorder, as has also been shown for physiologically regulated erythroid hyperplasia. However, the defect is quantitatively much more striking in experimental iron deficiency, and this and perhaps a similar defect in bone marrow cells appear to explain the decrease in net hemoglobin production that is characteristic of pathologic ineffective erythropoiesis.
D000747:Anemia, Hypochromic / Q000503:physiopathology*; D000818:Animals; D001663:Bilirubin / Q000096:biosynthesis*; D002247:Carbon Isotopes; D004920:Erythropoiesis; D005998:Glycine / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006454:Hemoglobins / Q000096:biosynthesis; D006461:Hemolysis; D007501:Iron / Q000378:metabolism; D007503:Iron Isotopes; D008297:Male; D051381:Rats; D012156:Reticulocytes / Q000378:metabolism*
D002247:Carbon Isotopes; D006454:Hemoglobins; D007503:Iron Isotopes; D006418:Heme; D007501:Iron; D001663:Bilirubin; D005998:Glycine