IL-4 INDUCES NEUTROPHILIC MATURATION OF HL-60 CELLS AND ACTIVATION OFHUMAN PERIPHERAL-BLOOD NEUTROPHILS

IL-4 is a T-helper cell derived cytokine that has effects on myelomono cytic cell maturation and activation. We have studied the effect of IL -4 on neutrophilic maturation using the cell line HL-60 and found that it has a profound effect on the maturation and activation of the cell line. The treatment of HL-60 cells with recombinant hu IL-4 (0.15 to 15.0 ng/ml) induced a shift in the percentage of HL-60 cells staining positive for chloroacetate esterase enzyme activity (indicating commit ment to the neutrophilic lineage). IL-4 increased surface expression o f the neutrophil-lineage antigen WEM G11, the complement receptors CR3 (CD11b) and CR1 (CD35), but not for the monocyte differentiation anti gen CD14. IL-4 treated HL-60 cells demonstrated enhanced Fc- and compl ement-mediated phagocytic capacity and increased hexose-monophosphate shunt activity. In addition, IL-4 was capable of sustaining the neutro phil maturation of HL-60 cells that had been pre-treated for 24 h with DMSO. To investigate the effect of IL-4 on the mature neutrophil, we studied freshly isolated and rested human peripheral blood neutrophils . In the absence of other stimuli, neutrophils were induced by IL-4 to have significantly elevated phagocytic responses. The response was sp ecific since treatment with anti-human IL-4 abolished phagocytic stimu lation. Finally, IL-4 treatment also stimulated resting neutrophils to migrate toward zymosan-activated serum (ZAS) and human IL-5. The resu lts demonstrate that IL-4 is a potent maturation factor for myelocytes to become neutrophils and that IL-4 can stimulate resting mature neut rophils.