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.
Novak-Hofer
I
I
Paul Scherrer Institute, Villigen-PSI, Switzerland.
Bläuenstein
P
P
Schubiger
P A
PA
D000906:Antibodies; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000096:biosynthesis*; D001666:Binding Sites, Antibody; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism; D003720:Densitometry; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D003574:Cytochrome c Group; D006023:Glycoproteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004121:Dimethyl Sulfoxide