Monoclonal antibodies to novel myeloid antigens reveal human neutrophil heterogeneity

Abstract

Three cytotoxic murine monoclonal antibodies that recognize myeloid-specific antigens have been produced by immunization with normal human neutrophils or myeloblasts from a patient with acute myelomonocytic leukemia. Two of these, PMN 6 and PMN 29, are specific for neutrophils; the third monoclonal antibody, AML-2-23, is reactive with the majority of normal monocytes as well as a subpopulation of mature neutrophils. Although neutrophils from all individuals tested expressed these antigens, cytofluorographic analysis revealed that the percentage of cells bearing the PMN 6 and AML-2-23 antigens varied among individuals. Significant additional heterogeneity in the density of each antigen among antigen-bearing cells was also observed. All three antibodies efficiently mediated complement-dependent cytotoxicity of acute myelocytic leukemia cells yet were unreactive with lymphocytic leukemia cells. Neutrophil cytotoxicity was mediated by PMN 6 and PMN 29 but not by AML-2-23. On the other hand, AML-2-23, but not PMN 6 or PMN 29, was cytotoxic for normal monocytes and macrophages. These monoclonal antibodies may be of value in the study of normal neutrophil function and differentiation and may have clinical utility in diagnosis and therapy of myeloid leukemia.