Fetal Hemoglobin Restriction to a Few Erythrocytes (F Cells) in Normal Human Adults

Boyer, Samuel H.; Belding, Thomas K.; Margolet, Louise; Noyes, Andrea N.

doi:10.1126/science.804182

Cited by 224 publications

(98 citation statements)

References 13 publications

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“…The increase of HbF in pregnant women is the result of alterations in maternal erythropoiesis and not due to transplacental bleeding from the fetus (9)(10)(11). In the present study, culturing peripheral blood BFU-E in vitro, HbF synthesis is increased to as high as 25% of the total hemoglobin produced in erythroid cell cultures, although the degree of augmentation varies considerably.…”

Section: Methodsmentioning

confidence: 64%

“…These erythroblasts, derived from normal adult individuals, synthesize a substantial amount of fetal hemoglobin (6)(7)(8). Because HbF is increased in maternal peripheral blood during pregnancy (9)(10)(11), the present investigation was undertaken to determine if peripheral blood BFU-E in pregnant women have an increased capacity for HbF production in culture and to study the pattern of HbF synthesis during erythroid cell maturation in vitro. Evidence is presented that the capacity for HbF production by peripheral blood BFU-E in vitro is not altered during pregnancy.…”

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confidence: 99%

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Proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation.

Chui¹,

Wong²,

Enkin³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

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Peripheral blood mononuclear cells from pregnant and postpartum women were cultured in vitro with erythropoietin. Burst-forming unit (BFU-E)derived erythroid colonies composed of immature erythroblasts with low hemoglobin contents were observed by day 8 of culture. By day 12 of culture, numerous BFU-E-derived erythroid colonies with high hemoglobin contents were present. The Y/(y + f) globin synthetic ratio was approximately 12% in the early cultures and 6% in the late cultures, indicating that the proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation. These studies also reveal that the capacity for fetal hemoglobin production by peripheral blood BFU-E in vitro is not altered during pregnancy.The major hemoglobin in humans during intrauterine life is fetal hemoglobin, a2Y2. Adult hemoglobin, a232, is first detected at around the 10th week of gestation and accounts for approximately 10% of all hemoglobins present until about the 30th week of gestation, when increasing amounts of adult hemoglobin are produced (1). By the time the infant is 6 months old, most of the hemoglobin present is adult hemoglobin (2). The mechanisms for the switching of hemoglobins during fetal development are presently not clear (3). These orderly ontogenetic changes provide an excellent model for studying gene regulation and expression. In addition, elucidation of the mechanisms for hemoglobin switching can provide a potentially useful approach to the therapy of patients with genetic disorders involving the j globin chain.Immature erythroid stem cells, burst-forming units that respond to erythropoietin (BFU-E), are present in adult human peripheral blood and can proliferate and differentiate into large colonies of erythroblasts in vitro (4, 5). These erythroblasts, derived from normal adult individuals, synthesize a substantial amount of fetal hemoglobin (6-8). Because HbF is increased in maternal peripheral blood during pregnancy (9-11), the present investigation was undertaken to determine if peripheral blood BFU-E in pregnant women have an increased capacity for HbF production in culture and to study the pattern of HbF synthesis during erythroid cell maturation in vitro. Evidence is presented that the capacity for HbF production by peripheral blood BFU-E in vitro is not altered during pregnancy. These studies also reveal that the proportion of HbF synthesis decreases during erythroid cell maturation. A preliminary report of these studies has been published elsewhere (12). METHODSSubjects. Forty-four pregnant and postpartum (3-7 months) women were studied. All women were healthy and had no known diseases or complications. Appropriate consent was obtained. [50][51][52][53][54][55][56][57][58][59][60] Ci/mmol; 1 Ci = 3.7 X 1010 becquerels), obtained from New England Nuclear, was added to each plasma clot on either day 6 or day 7, and either day 11 or day 12 of culture. Twenty-four hours later, 10 plasma clots thus labeled were pooled and washed twice with phosphate-buffered saline. Three milligrams o...

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Section: Methodsmentioning

confidence: 64%

mentioning

confidence: 99%

Proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation.

Chui¹,

Wong²,

Enkin³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

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“…Fetal red cells during the 1 st trimester exclusively contain Hb F [11], while adult F cells contain both Hb F and Hb A, with a variable proportion of Hb F ranging up to 25% of the total Hb in adult F cells [12]. The correlation between %Hb F level and %F cells among non-pregnant adult subjects suggests that an increase in number of adult F cells by 1.0% results in an increase in %Hb F by 0.1% [13] implying that Hb F accounts for an approximately 10% of the total Hb in adult F cells.…”

Section: Discussionmentioning

confidence: 99%

Changes in hemoglobin F levels in pregnant women unaffected by clinical fetomaternal hemorrhage

Yamada¹,

Morikawa²,

Yamada³

et al. 2013

Clinica Chimica Acta

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Complete automation of high-performance liquid chromatography (HPLC) for determination of hemoglobin F (%Hb F) and hemoglobin A1c (%Hb A1c) levels has made this procedure available in many clinical laboratories. However, the physiological changes in %Hb F during pregnancy and the effects of physiological and supraphysiological levels of %Hb A1c on measurement of %Hb F have not been studied extensively. Simultaneous determination of %Hb F and %Hb A1c was conducted in 490 blood samples obtained before (n = 21), during 1 st (n = 150), 2 nd (n = 116), and 3 rd (n = 192) trimesters of pregnancy, and postpartum (n = 11) from 357 women, including 60 women with hyperglycemia but unaffected by clinical fetomaternal hemorrhage, by HPLC. Mean (SD) Hb F levels were 0.71% (0.25%) before pregnancy. The value of 0.82% (0.47%) during 1 st trimester decreased significantly to 0.66% (0.35%) during 2 nd trimester and to 0.58% (0.38%) during 3 rd trimester. The level was 0.62% (0.31%) approximately one year after delivery. Thus, %Hb F was highest during 1 st trimester of pregnancy. The effects of varied %Hb A1c levels on %Hb F measurements were clinically negligible. Our data may be used as reference intervals of %Hb F determined with HPLC during pregnancy.

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“…Hb F expression, restricted to a subset of erythrocytes called F Cells, varies with genetic and environmental factors [12,31]. It is estimated that eighty-nine percent of adult Hb F and F cell variance is due to heritable factors [30] and the XmnI polymorphism (C→T) at position −158 of the HBG2 promoter accounts for the greatest single share of this genetic variability [28,94].…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

Perry

Gearhart

Wiener

et al. 2008

Neurobiology of Aging

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From a normal human brain phage display library screen we identified the gamma (A)-globin chain of fetal hemoglobin (Hb F) as a protein that bound strongly to Aβ1-42. We showed the oxidized form 1 These authors are co-corresponding authors for all stages of refereeing and publication and contributed equally to this work. Rodney T. Perry; Rm. 210H, 1665 University Blvd.; University of Alabama at Birmingham, Birmingham, USA; Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure Statement:I so state for myself and on behalf of the other authors on the manuscript, Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease, that we have no conflicts and sources of funding that influence the results of this paper, the data is not published or submitted elsewhere, and that appropriate approval and procedures were used concerning human subjects. I also verify that all authors on this manuscript have reviewed the contents of the manuscript, approve of its contents, and validate the accuracy of the data. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript of adult Hb (metHb A) binds with greater affinity to Aβ1-42 than metHb F. MetHb is more toxic than oxyhemoglobin because it loses its heme group more readily. Free Hb and heme readily damage vascular endothelial cells similar to Alzheimer's disease (AD) vascular pathology. The XmnI polymorphism (C→T) at −158 of the gamma (G)-globin promoter region can contribute to increased Hb F expression. Using family-based association testing, we found a significant protective association of this polymorphism in the NIMH sibling dataset (n=489) in families, with at least two affected and one unaffected sibling (p=0.006), with an age of onset >50 years (p=0.010) and >65 years (p=0.013), and families not homozygous for the APOE4 allele (p=0.041). We hypothesize that Hb F may be less toxic than adult Hb in its interaction with Aβ and may protect against the development of AD.

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Fetal Hemoglobin Restriction to a Few Erythrocytes (F Cells) in Normal Human Adults

Cited by 224 publications

References 13 publications

Proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation.

Proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation.

Changes in hemoglobin F levels in pregnant women unaffected by clinical fetomaternal hemorrhage

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

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