Evidence for a role of the Na⁺/H⁺ exchanger in the colony‐stimulating‐factor‐induced ornithine decarboxylase activity and proliferation of the human cell line M‐07e

The subclone M‐07e, derived from the interleukin‐3 (IL‐3)‐responsive human myeloid cell line M‐07, is strictly dependent on either IL‐3 or granulocyte‐macrophage‐colony‐stimulating factor (GM‐CSF) for its growth and survival. This cell line may be regarded as a candidate model to investigate the poorly understood events triggered by growth factors binding to human hemopoietic cells. Both IL‐3 and GM‐CSF induce in M‐07e cells an increase of ornithine decarboxylase (ODC) activity, which reaches its maximum at 24–30 h and fully depends on de novo protein synthesis. The growth factors do not elicit translocation of protein kinase C to the membrane; thus a role of the kinase in ODC induction is ruled out. An amiloride‐inhibitable Na⁺/H⁺ exchanger is present in the membrane of M‐07e cells; its apparent Km for extracellular Na⁺ is 47.77 mM; and its activity is greatly enhanced when the cytoplasm is acidified. Growth‐factor‐evoked ODC activation and DNA synthesis are blocked in a dose‐ and time‐dependent manner when M‐07e cells are incubated with ethylispropyl‐amiloride, a specific inhibitor of Na⁺/H⁺ exchanger. The exchanger does not appear to be directly activated by IL‐3 or GM‐CSF, but its operation is strictly required for the biological effects of these growth factors on M‐07e cell line.