Antagonism between interleukin 3 and erythropoietin in mice with azidothymidine-induced anemia and in bone marrow endothelial cells.
Azidothymidine (AZT)-induced anemia in mice can be reversed by the administration of IGF-IL-3 (fusion protein of insulin-like growth factor II (IGF II) and interleukin 3). Although interleukin 3 (IL-3) and erythropoietin (EPO) are known to act synergistically on hematopoietic cell proliferation in vitro, injection of IGF-IL-3 and EPO in AZT-treated mice resulted in a reduction of red cells and an increase of plasma EPO levels as compared to animals treated with IGF-IL-3 or EPO alone. We tested the hypothesis that the antagonistic effect of IL-3 and EPO on erythroid cells may be mediated by endothelial cells. Bovine liver erythroid cells were cultured on monolayers of human bone marrow endothelial cells previously treated with EPO and IGF-IL-3. There was a significant reduction of thymidine incorporation into both erythroid and endothelial cells in cultures pre-treated with IGF-IL-3 and EPO. Endothelial cell culture supernatants separated by ultrafiltration and ultracentrifugation from cells treated with EPO and IL-3 significantly reduced thymidine incorporation into erythroid cells as compared to identical fractions obtained from the media of cells cultured with EPO alone. These results suggest that endothelial cells treated simultaneously with EPO and IL-3 have a negative effect on erythroid cell production.
DiFalco
Marcos R
MR
Department of Experimental Medicine, Endocrine Laboratory, McGill University Health Centre, Montreal, Canada.
Congote
Luis Fernando
LF
D000740:Anemia / Q000139:chemically induced*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism*; D004921:Erythropoietin / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism*; D019169:Jurkat Cells; D008099:Liver / Q000166:cytology; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D015215:Zidovudine
D000963:Antimetabolites; D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D004921:Erythropoietin; D015215:Zidovudine; D007335:Insulin-Like Growth Factor II; D013936:Thymidine