Suppression and Potentiation of Mouse Hematopoietic Progenitor Cell Proliferation by Ouabain

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 10–6–10–12M 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.