Clonal assays for CFU-S, CFU-C, BFU-E, and CFU-E were employed to evaluate the effect of ouabain on the proliferation of mouse hematopoietic progenitor cells. Preincubation of bone marrow cells with ouabain at concentrations of 10–6–10–12 M suppressed the proliferation of CFU-S as measured by the spleen colony assay. At 10–9M ouabain, spleen colony formation was inhibited by more than 95%. When included in soft agar cultures of bone marrow cells, ouabain suppressed the proliferation of CFU-C in a complex fashion. At 10–4M ouabain, colony formation was suppressed by 70%, while at 10–6M ouabain, CFU-C proliferation was normal. At 10–9M ouabain, however, the number of colonies formed was only 70% of normal, and complete recovery was not obtained at 10–12M ouabain. The number of colonies formed by BFU-E and CFU-E in plasma clot cultures was also diminished in the presence of 10–4M ouabain. In contrast to its effect on CFU-S and CFU-C, however, 10–9M ouabain enhanced BFU-E colony formation by 200% and CFU-E colony formation by 35%; at 10–12M ouabain, CFU-E proliferation was unaffected by the drug. These data indicate that mouse CFU-S, CFU-C, BFU-E, and CFU-E require a functional membrane-bound Na+K+ATPase for proliferation; that these progenitor cells differ in their response to ouabain and finally, that ouabain at concentrations below that (10–6M) considered necessary to inhibit membrane-bound Na+K+ ATPase can influence the proliferation of mouse hematopoietic progenitor cells.
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Spivak et al. (1980) studied this question.