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Research Article Free access | 10.1172/JCI110197

Identification of Spermine as an Inhibitor of Erythropoiesis in Patients with Chronic Renal Failure

Heinz W. Radtke, Arvind B. Rege, Max B. Lamarche, Dagmar Bartos, Frantisek Bartos, Robert A. Campbell, and James W. Fisher

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Renal Dialysis Unit, New Orleans Charity Hospital, New Orleans, Louisiana 70112

Pediatric Renal-Metabolic Laboratory, The Department of Pediatrics, University of Oregon, Health Sciences Center, Portland, Oregon 97201

Find articles by Radtke, H. in: PubMed | Google Scholar

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Renal Dialysis Unit, New Orleans Charity Hospital, New Orleans, Louisiana 70112

Pediatric Renal-Metabolic Laboratory, The Department of Pediatrics, University of Oregon, Health Sciences Center, Portland, Oregon 97201

Find articles by Rege, A. in: PubMed | Google Scholar

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Renal Dialysis Unit, New Orleans Charity Hospital, New Orleans, Louisiana 70112

Pediatric Renal-Metabolic Laboratory, The Department of Pediatrics, University of Oregon, Health Sciences Center, Portland, Oregon 97201

Find articles by Lamarche, M. in: PubMed | Google Scholar

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Renal Dialysis Unit, New Orleans Charity Hospital, New Orleans, Louisiana 70112

Pediatric Renal-Metabolic Laboratory, The Department of Pediatrics, University of Oregon, Health Sciences Center, Portland, Oregon 97201

Find articles by Bartos, D. in: PubMed | Google Scholar

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Renal Dialysis Unit, New Orleans Charity Hospital, New Orleans, Louisiana 70112

Pediatric Renal-Metabolic Laboratory, The Department of Pediatrics, University of Oregon, Health Sciences Center, Portland, Oregon 97201

Find articles by Bartos, F. in: PubMed | Google Scholar

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Renal Dialysis Unit, New Orleans Charity Hospital, New Orleans, Louisiana 70112

Pediatric Renal-Metabolic Laboratory, The Department of Pediatrics, University of Oregon, Health Sciences Center, Portland, Oregon 97201

Find articles by Campbell, R. in: PubMed | Google Scholar

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Renal Dialysis Unit, New Orleans Charity Hospital, New Orleans, Louisiana 70112

Pediatric Renal-Metabolic Laboratory, The Department of Pediatrics, University of Oregon, Health Sciences Center, Portland, Oregon 97201

Find articles by Fisher, J. in: PubMed | Google Scholar

Published June 1, 1981 - More info

Published in Volume 67, Issue 6 on June 1, 1981
J Clin Invest. 1981;67(6):1623–1629. https://doi.org/10.1172/JCI110197.
© 1981 The American Society for Clinical Investigation
Published June 1, 1981 - Version history
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Abstract

Fetal mouse liver and normal human bone marrow cell cultures were used for studies on the inhibition of erythroid colony formation (CFU-E) by sera from anemic patients with end-stage renal failure and the polyamine spermine. Sera from each of eight predialysis uremic anemic patients with end-stage renal failure produced a significant (P < 0.001) inhibition of erythroid colony formation in the fetal mouse liver cell cultures when compared to sera from normal human volunteers. In vivo or in vitro dialysis of the uremic sera with a 3,500-dalton exclusion limit membrane removed the inhibitor from uremic sera. The uremic serum dialysate provided by the membrane fractionation was significantly inhibitory in the erythroid cell cultures. When this dialysate was applied to gel filtration chromatography (Bio-Gel P-2) the inhibitor was found to be in the same molecular weight range as [14C]spermine. The polyamine spermine produced a dose-related inhibition of erythroid colony formation (CFU-E) in fetal mouse liver and normal human bone marrow cultures. Thus, the following evidence is provided that the in vitro inhibitor of erythropoiesis found in chronic renal failure patients' sera is identical with the polyamine spermine: (a) the inhibitor and radiolabeled spermine appeared in identical Bio-Gel P-2 effluent fractions; (b) when spermine was added to normal human sera at concentrations reported in sera of uremic patients, and studied in both the fetal mouse liver cell culture and normal human bone marrow cultures, a dose-related inhibition of erythroid colony (CFU-E) formation was noted; and (c) the inhibitory effects of crude uremic serum, uremic serum dialysate, and fractions of uremic serum dialysate from a Bio-Gel column, on erythroid colony formation were completely abolished by the addition of a specific rabbit antiserum to spermine.

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