Comparison of hemin enhancement of burst-forming units-erythroid clonal efficiency by progenitor cells from normal and HIV-infected patients.
The ability of peripheral-blood hematopoietic progenitor cells from AIDS patients and normal controls to respond to erythropoietin (Epo) was assessed for burst-forming units-erythroid (BFU-E). BFU-E colony formation from AIDS patients' peripheral blood responded to a wide range of Epo concentrations (0.5-4 U) in a similar manner as erythroid progenitors obtained from normal peripheral blood. The optimum dose response of BFU-E to Epo was 2 U which resulted in generation of 71 +/- 4 BFU-E in AIDS patients (n = 10), as compared to 77 +/- 5 BFU-E in normal donors (n = 3). The optimum concentration range of hemin enhancement of erythroid progenitor BFU-E was 10-50 microM. In all instances, Epo was essential for BFU-E growth. Inclusion of hemin at a concentration of 10 microM in AIDS patients' peripheral-blood erythroid progenitor cells resulted in enhancement of BFU-E by 136-215%. Similarly, inclusion of hemin (10-100 microM) in normal bone marrow erythroid progenitor cell cultures resulted in enhancement of BFU-E. Inclusion of an equivalent amount of iron or tin protoporphyrin to progenitors cells from AIDS patients' peripheral blood had no effect on the number of colonies observed. On the other hand, inclusion of another heme analogue, zinc protoporphyrin, in AIDS or normal cultures resulted in a 50% suppression of BFU-E colony formation. These results demonstrate that peripheral-blood mononuclear cells from AIDS patients retain the capacity to generate erythroid precursors such as BFU-E in the presence of Epo, and that hemin has a specific enhancement effect on growth of BFU-E colony formation obtained from peripheral blood or bone marrow cells.
Abraham
N G
NG
Department of Medicine, New York Medical College, Valhalla.
Mathew
A
A
Jiang
S
S
Lutton
J D
JD
Nishimura
M
M
Chertkov
J L
JL
Levere
R D
RD
D000386:AIDS-Related Complex / Q000097:blood; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood; D000328:Adult; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D015658:HIV Infections / Q000097:blood*; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D009894:Opportunistic Infections / Q000097:blood; D011524:Protoporphyrins / Q000494:pharmacology; D012016:Reference Values
D011524:Protoporphyrins; D004921:Erythropoietin; D006427:Hemin