Effects of oxidative stress on human erythroid colony formation: Modulation by gamma-interferon.
Evidence of increased oxidative stress is a hallmark of many chronic diseases associated with anemia. The current study was undertaken to evaluate the effects of oxidative stress on erythroid colony formation in vitro by bone marrow light density mononuclear cells (LDMN) and by peripheral blood derived cells enriched for erythroid colony forming units (CFU-E), and how these effects can be modified by a cytokine implicated in the anemia of chronic disease. When blood-derived and marrow cells were cultured with 50 microM H(2)O(2), CFU-E colony formation by blood-derived cells but not by marrow cells was significantly inhibited, suggesting a protective effect of marrow accessory cells. This inhibitory effect on peripheral blood-derived CFU-E was shown to be caspase-dependent. rhgammaIFN at concentrations which did not inhibit CFU-E colony formation sensitized LDMN marrow cells to inhibition by H(2)O(2). Exposure of LDMN marrow cells to rhgammaIFN at concentrations of 10 U/mL or higher significantly decreased the concentration of thioredoxin (Trx) in cell supernatant. Addition of recombinant Trx to LDMN marrow cells cultured with H(2)O(2) and rhgammaIFN partially (although not completely) reversed inhibition of CFU-E colony formation. These findings suggest that inflammatory cytokines implicated in the pathogenesis of the anemia of chronic disease may exert their effects at least in part through modulation of oxidative stress.
Dallalio
Gail
G
Hematology/Oncology Division, Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA.
Means
Robert T
RT
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D018384:Oxidative Stress
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases