Effects of hemin on erythropoiesis

Abstract

It is clear that in vitro hemin increases the number of blood BFU-E derived colonies from normal donors. This occurs with sickle donors as well, despite the increased levels of hemin in vivo in these patients. The effect of hemin on relative γ globin synthesis is inconsistent, however. In a few cases, delayed addition of hemin led to increased γ globin synthesis. In time course studies of cultures from normal donors, hemin added on day 0 shifted the day of peak colony number from 13-14 to 16-20 days. The temporal decline in γ globin synthesis was not altered. In cultures from sickle donors we found that the time for maximal colony number was later than in normals, occurring at 16-20 days even without hemin, and was not further delayed by hemin. The relative proportion of γ globin synthesis was higher on day 14 in the sickle than the normal cultures, and the temporal decline was somewhat slowed in the sickle cultures by hemin. The elevated γ synthesis and the later time for peak colony growth in the sickle cultures suggest that the erythroid progenitors in the blood of the sickle patients are less mature than those from normal individuals. There are several possible explanations for the detection of increased numbers of colonies in cultures containing hemin. Hemin may delay the final maturation of erythroblasts within erythroid colonies, thus shifting the time of maximal growth. It may also increase the extent of final maturation, leading to more complete hemoglobinization of the erythroblasts within the colonies, and thus increasing the number of colonies that are eventually recognized as erythroid. The colonies appear to be larger in the presence of hemin, again possibly related to more complete hemoglobinization. Hemin might also lead to differentiation and maturation from immature BFU-E, which would not have developed into recognizable colonies without hemin.