Heterogeneity in responses of human blood monocytes to granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has stimulatory effects on various monocyte functions. We examined whether all or only some blood monocytes could respond to GM-CSF. Monocytes from peripheral blood of healthy donors were separated by size into five fractions by counter-flow centrifugal elutriation (CCE). The phagocytic activities of monocytes in these fractions depended on the size of the cells. On activation by bacteria-derived stimuli, these fractions showed similar responses of production of monokines such as interleukin-1 (IL-i ) and tumor necrosis factor (TNF) and cytotoxicity against allogeneic tumor cells. On treatment of these fractions with optimal concentration of GM-CSF, fractions 3, 4, and 5 showed tumoricidal activity and produced cell-associated IL-i , fraction 3 producing the most, whereas release of IL-i and TNF in the supernatant was not observed. The cell-associated IL-i was identified as IL-i a, not IL-i �, by neutralizing tests with antisera against lL-ix and IL-i �. GM-CSF also induced the proliferative and colony-forming responses of medium and large monocytes. These observations suggest that adoptive therapy with macrophage progenitor cells in peripheral blood may be useful in combination with GM-CSF for treatment of monocytopenia after chemotherapy or radiation therapy.