[Possible role of soluble erythropoietin receptors in renal anemia].
Recombinant human erythropoietin(rHuEpo) is effective for the treatment of renal anemia associated with chronic renal failure(CRF). However, we have encountered some patients with CRF who have sometimes developed a resistance to rHuEpo. This resistance can be due to iron or folate deficiency, aluminum toxicity, hyperparathyroidism, or auto-antibodies for rHuEpo. In this study, we focused on the soluble erythropoietin receptor(sEpoR), which can bind to rHuEpo. To demonstrate the possibility that the sweeping of rHuEpo by sEpoR results in resistance to rHuEpo, we performed a bioassay using the rHuEpo-dependent cell line, UT7/EPO. The results showed that recombinant mouse sEpoR(rmsEpoR) can reduce the proliferation of UT7/EPO induced by rHuEpo in a dose-dependent manner. We consider that this cell line could be a useful tool in a bioassay to detect the inhibitory factor(s) against Epo. We selected sera from three groups of patients with renal anemia associated with CRF who were receiving hemodialysis three times a week: the first was a patient group that needed a high dose of rHuEpo(7,500-9,000 unit/dialysis), the second was a patient group that needed an intermediate dose of rHuEpo (4,500 unit/dialysis), the third was a patient group that needed a low dose of rHuEpo(below 1,500 unit/dialysis). Interestingly, the proliferation of UT7/EPO determined with [3H]-thymidine incorporation was reduced by the addition of sera from the first group, but not by the addition of sera from the third group. These results suggested that serum sEpoR may play an important role in signal transduction via EpoR on erythroid progenitor in CRF patients.
Sakaguchi
Mika
M
Department of Internal Medicine, Division of Hematology, Nephrology, and Rheumatology, Kinki University School of Medicine, Osaka, Japan.
Maeda
Yasuhiro
Y
Naiki
Yoshito
Y
Hasegawa
Hirofumi
H
Kanamaru
Akihisa
A
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood* / Q000209:etiology; D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D004921:Erythropoietin / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications; D051379:Mice; D008875:Middle Aged; D017467:Receptors, Erythropoietin / Q000097:blood / Q000502:physiology*; D011994:Recombinant Proteins; D015398:Signal Transduction; D012995:Solubility
D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin