Granulocyte-Colony Stimulating Factor, Granulocyte-Macrophage Colony Stimulating Factor and Interleukin 4 Induce Differentiation in the U-937 Human Monocytic Leukemia Cell Line

Abstract

We studied the effect of TPA, G-CSF, GM-CSF, conditioned medium from 5637 cells (CM5637) and IL-4 on U-937 cell line proliferation and differentiation. Flow cytometry analysis showed that the expression of the CD 14 cell surface antigen, initially detected in 90% of the cells, decreased when the cells were cultured with either G-CSF, GM-CSF, CM5637, or IL-4. The CD1 lc expression only decreased by exposure to GM-CSF and IL-4. The cells also showed a decrease in alpha-naph-thylesterase (α-NAE) activity and an increase in peroxidase (Px) activity in the GM-CSF supplemented cultures. Remarkable changes in cell morphology were also observed. IL-4 induced morphologic features resembling histiocytic-like cells positive for the expression of α-NAE and negative for Px. GM-CSF induced cells with pseudopods, negative for α-NAE expression and positive for Px. TPA effect on U-937 cells was similar to that observed with GM-CSF. No proliferative response was detected with any of the factors assayed. These results suggest that GM-CSF and IL-4 can promote distinct changes in the differentiative pathway of U-937 cells, as evidenced by the marked morphological, immunological and cytochemical changes observed in the cell cultures.

Key Words:

• U-937 cell line
• myeloid differentiation
• G-CSF
• GM-CSF
• IL-4 CDllc
• CD14