Role of Na+/H+ exchange in the granulocyte-macrophage colony-stimulating factor-dependent growth of a leukemic cell line

✍ Scribed by Daniele Caracciolo; Antonella Pannocchia; Silvia Treves; Dario Ghigo; Eugenio Gallo; Corrado Tarella; Federico Bussolino; Franco Turrini; Giacomo Tamponi; Amalia Bosia

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 764 KB
• Volume: 143
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041430118

✦ Synopsis

The growth of the human leukemia cell line AML-193 in a serum-free medium is strictly dependent o n the presence of the cytokine granulocyte-macrophage COIL ony-stimulating factor (GM-CSF), which is one of the major regulators of the myelomonocytic lineage. At present, little is known about the mechanisms by which this growth factor transduces the signal intracellularly. The results of this study demonstrate that GM-CSF needs the operation of a Na+/H+ exchanger, which is located in the plasma membrane of almost every vertebrate cell. In fact, the GM-CSF-dependent proliferation of AML-193 cells is strongly reduced in the presence of the amiloride analog EIPA, a specific inhibitor of the Na+/H' exchanger. When acidified, AML-193 cells are able to recover the original pH, in a Na+-dependent and EIPA-inhibitable way; this demonstrates for the first time the presence of the N a + / H + exchanger in these cells. Finally, GM-CSF, at doses superimposable to those needed for triggering proliferation, induces in AML-193 cells a sustained alkalinization, which is dependent on a operating Na+/H+ exchange, as it is inhibited by EIPA. These results suggest that GM-CSF, like other growth factors in other cell systems, exerts its mitogenic activity in AML-193 cells by inducing a N a f / H i exchanger-mediated rise in pHi.