Suppression and potentiation of mouse hematopoietic progenitor cell proliferation by ouabain.

CIonal 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 101_1012 M suppressed the proliferation of CFU-S as measured by the spleen colony assay. At lO9Mouabain, 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 1 04M ouabain, colony formation was suppressed by 70%, while at 1 0#{176}M ouabain, CFU-C proliferation was normal. At 109M ouabain, however, the number of colonies formed was only 70% of normal, and complete recovery was not obtained at 1012M ouabain. The number of colonies formed by BFU-E and CFU-E in plasma clot cultures was also diminished in the presence of 1 04M ouabain. In contrast to its effect on CFU-S and CFU-C. however, 109M ouabain enhanced BFU-E colony formation by 200% and CFU-E colony formation by 35%; at 10’2M 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 (10M) considered necessary to inhibit membrane-bound Na K ATPase can influence the proliferation of mouse hematopoietic progenitor cells.