TRANSMEMBRANE POTENTIAL RESPONSES DURING HL-60 PROMYELOCYTE DIFFERENTIATION

Myeloid cells, including granulocytes and monocyte/macrophages, are im portant in disease-associated inflammatory reactions. These cells come from a common progenitor, the promyelocyte. The human promyelocytic c ell line, HL-60, can be induced to terminally differentiate into granu locytes or monocyte/macrophages in a controlled fashion providing a mo del to study various aspects of myelomonocytic differentiation. The ex pression of several ion channels is controlled in HL-60 cells in a dif ferentiation specific pattern. The purpose of this study was to determ ine if lineage-specific ion channel expression during HL-60 differenti ation resulted in differences in functional responses to external stim uli. This was investigated by examining transmembrane potential respon ses in HL-60 promyelocytes, HL-60-derived polymorphonuclear cells (PMN s), and monocytes to various stimuli using the transmembrane potential sensitive dye, diSBAC(2)-(3). Exposure of HL-60 promyelocytes to iono mycin or ATP produced a membrane hyperpolarization. Studies using ion substitutions and ion channel blockers indicate that the hyperpolariza tion was mediated by K-Ca channels. During HL-60 promyelocyte differen tiation to PMNs, the membrane potential response to ionomycin and ATP shifted from a hyperpolarization to a depolarization over 7 days. Conv ersely, HL-60-derived monocytes exhibited a membrane hyperpolarization in response to ionomycin and ATP. HL-60-derived monocytes also exhibi t a Cl- conductance specifically induced by ATP. Lineage-specific expr ession of ion channels during HL-60 cell differentiation is important in determining the transmembrane potential response of these cells. Th is may be translated into functional responses of various myelomonocyt ic cells during disease-associated inflammatory reactions. (C) 1996 Wi ley-Liss, Inc.