Regulation of the cell surface expression of a nonspecific cross-reacting antigen variant during differentiation of HL-60 cells

The expression of a nonspecific cross-reacting antigen (NCA) species on the cell surface of the human promyelocytic leukemia cell line HL-60 was investigated via binding of 125I-labeled carcinoembryonic antigen (CEA) and NCA-specific monoclonal antibodies (Mabs). Very low specific binding of the CEA-specific Mab35 was found, whereas the CEA- and NCA-recognizing Mab47 showed 20-fold higher binding. The number of binding sites for Mab47 on HL-60 cells is lower than on normal granulocytes and is modulated by inducers of cellular differentiation and growth. Dimethylsulfoxide (DMSO), an inducer of neutrophilic differentiation, increased Mab47 binding in a time-dependent manner up to 4-fold after 7 days. In contrast, phorbol-12-myristate-13-acetate which induces differentiation into monocyte/macrophages led to a loss of binding sites. Mab47 binding was also decreased by granulocyte-macrophage colony-stimulating factor and this effect was enhanced in the presence of DMSO during the first 3 days of DMSO treatment. It is concluded that agents affecting neutrophilic differentiation or cell growth act in an opposite manner on NCA expression of HL-60 cells. NCA expression is not crucial for neutrophilic differentiation because it can be suppressed by granulocyte-macrophage colony-stimulating factor early in the differentiation program without affecting cell maturation.