Transferrin receptor-mediated suppression of in vitro hematopoiesis by transferrin-gallium.
The expression of transferrin receptors on cells is felt to reflect iron requirements for proliferation or for hemoglobin production. We have recently shown that transferrin-gallium (Tf-Ga) complexes bind to cellular transferrin receptors and inhibit cellular iron incorporation. In this study, Tf-Ga in a dose-dependent manner inhibited the growth of erythroid (erythroid burst-forming units [BFU-E]-derived), granulocyte-macrophage (granulocyte-macrophage colony-forming units [CFU-GM]-derived) and mixed (mixed CFU [CFU-GEMM]-derived) hematopoietic colonies. Although major differences in the response of the different progenitor cells to Tf-Ga were not seen, CFU-GEMM-derived colonies appeared to be more sensitive to growth inhibition by Tf-Ga. The inhibitory effects on colony growth were reversible after 48 h of exposure of marrow cells to Tf-Ga, suggesting that the initial effects of Tf-Ga were mainly cytostatic and that continuous exposure of cells to Tf-Ga was required for maximal growth inhibition. Transferrin-iron (Tf-Fe) added to the Tf-Ga-containing cultures restored colony growth; however, this effect was best seen when Tf-Fe was added at day 0 of incubation. Tf-Fe added on days 3 or 7 failed to restore GEMM colonies and restored only a fraction of BFU-E and GM colonies. Tf-Ga appears to inhibit hematopoietic progenitor cell growth by interfering with cellular iron utilization during an early phase of progenitor cell proliferation. The use of Tf-Ga may allow further exploration of the role of iron and the Tf receptor in the regulation of hematopoietic progenitor cell growth.
Chitambar
C R
CR
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Craig
A
A
Ash
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RC
D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005708:Gallium / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000502:physiology; D011990:Receptors, Transferrin / Q000502:physiology*; D014168:Transferrin / Q000494:pharmacology*
D011990:Receptors, Transferrin; D014168:Transferrin; D005708:Gallium; D007501:Iron