Activation of Antibody-dependent Cell-mediated Cytotoxicity of Human Neutrophils and Eosinophils by Separate Colony-stimulating Factors

Semi-purified human colony-stimulating factors (CSF) powerfully enhanced the antibody-dependent cell-mediated cytotoxicity (ADCC) by metrizamide gradient-purified human neutrophils and eosinophils. The stimulation was observed on three different tumor targets, was rapid (less than 1 hr) in onset, and CSF-stimulated cells needed direct contact with targets for killing. A subspecies of human CSF, CSF-alpha, with eosinophil and granulocyte-macrophage (GM) colony-stimulating activity enhanced both eosinophil and neutrophil killing. In contrast, another subspecies of human CSF, CSF-beta, having only GM colony-stimulating activity, only enhanced neutrophil-mediated ADCC. These results support the notion that human CSF have two sites of action: i) the progenitor cell, where they stimulate a relatively slow process of differentiation, and ii) the mature cell, where they have a rapid action of increasing functional capacity. Furthermore, it seems the pattern of CSF receptors on progenitor cells is maintained throughout the lineage of such cells and serves to regulate the function of mature cells.