The Na+/H+ exchanger is an ion transport system present in the plasma membrane of most cells and constitutes a major regulator of intracellular pH in these cells. The importance of the exchanger goes beyond the regulation of intracellular pH in the overall cell maintenance. Activation of many cells is accompanied by internal alkalinization and activation of the exchanger. The role of the exchanger in the control of cell growth was also indicated by the decrease in tumorigenicity upon genetic alteration of the exchanger. We propose a detailed biochemical and functional characterization of the Na+/H+ exchanger in granulocytic cells with the following aims: 1) to understand the role of the exchanger in the response of granulocytes to inflammatory agents. 2) to understand the role of the exchanger in the process of granulocytic maturation. 3) to obtain antibodies that specifically react with the exchanger; these antibodies will be subsequently used for genetic identification of the exchanger. These studies will further our understanding of some of the physiologic changes a primitive cell needs to undergo in the process of granulocytic maturation. We will study two types of cells: human granulocytes and a promyelocytic cell line HL-60. In the presence of the appropriate stimulus HL-60 cells are induced to mature into granulocytes. Our studies are also of interest to the pharmacology of granulocytic cells.
