Differentiation of macrophage precursors to cells with LAK activity under the influence of CSF-1 and high dose IL-2

Mouse macrophage precursor cells with natural killer (NK) like activity were incubated with high dose IL-2. After 3 days of incubation, cells had developed from NK-like into LAK-like effector cells. Morphological studies revealed that LAK activity occured at the time when macrophage precursors with NK-like activity containing few cytoplasmic granules had further differentiated into cells with abundant azurophilic granules in their cytoplasma. Proliferation of macrophage-precursor derived NK/LAK-like cells was dependent on the presence of colony-stimulating factor, generation of cytoplasmic granules was induced by IL-2 in a dose dependent way. Flow cytometric analysis showed that macrophage precursor-derived LAK effectors were positive for NK 1.1 but almost negative for F4/80, when the same starting cell population was cultured in the presence of 200 U/ml Interferon gamma, proliferation was completely stopped and within 3 - 4 days all cells differentiated into mature macrophages express ing F4/80. In context with our previous data, we describe here a continuum of development from a granular macrophage precursors to granular cells with NK-like activity and further to cells with LAK activity under the influence of CSF-1 as growth factor and IL-2 as granule- and cytotoxicity-inducing factor.