INDUCTION OF DIFFERENTIATION INTO MONOCYTE MACROPHAGE CELL LINEAGE OFA HUMAN EOSINOPHILIC LEUKEMIA-CELL LINE EOL-1 BY SIMULTANEOUS STIMULATION WITH TUMOR NECROSIS FACTOR-A AND INTERFERON-GAMMA/

Human myeloid leukaemia cell lines have been shown to differentiate in to distinct cell lineages in vitro in response to several differentiat ion-inducing agents. A human eosinophilic leukaemia cell line, EoL-1, has been shown to differentiate into mature eosinophilic granulocytes by treatment with the culture supernatant of a human T-cell line, HIL- 3. In this study we have studied whether the EoL-1 cell line has poten tial to differentiate into cell lineage other than eosinophils. We fou nd that EoL-1 cells cultured in the presence of tumour necrosis factor (TNF)-alpha (10 u/ml) and interferon (IFN)-gamma (1000 u/ml) for 2-4 d differentiated into macrophage-like cells in morphology, and express ed CD14 antigen on their cell surface. It is possible that the small s ubpopulation of EoL-1 cells which contains non-specific esterase (NSE) activity may be preferentially differentiated by TNF-alpha and IFN-ga mma. To clarify this issue, we have cloned the EoL-1 cell line and obt ained NSE negative and positive sublines. Both EoL-1 sublines differen tiated into monocyte/macrophage-like cells, because: (a) EoL-1 subline s were induced to express CD14 antigen, and (b) they attached firmly t o the plastic wells; (c) after differentiation they became strongly po sitive for NSE staining, and secreted TNF-alpha in response to the sti mulation with lipopolysaccharide; and (d) they exhibited potent phagoc ytic activity. Therefore, we found that the EoL-1 cell line has the ab ility to differentiate not only into mature eosinophilic cells but als o into monocyte/macrophage cell lineage, suggesting that EoL-1 cells r epresent immature cells with ability to differentiate into multiple ce ll lineages.