IL-4 induces neutrophilic maturation of HL-60 cells and activation of human peripheral blood neutrophils.
IL-4 is a T-helper cell derived cytokine that has effects on myelomonocytic 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 commitment to the neutrophilic lineage). IL-4 increased surface expression of the neutrophil-lineage antigen WEM G11, the complement receptors CR3 (CD11b) and CR1 (CD35), but not for the monocyte differentiation antigen CD14. IL-4 treated HL-60 cells demonstrated enhanced Fc- and complement-mediated phagocytic capacity and increased hexose-monophosphate shunt activity. In addition, IL-4 was capable of sustaining the neutrophil 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 specific since treatment with anti-human IL-4 abolished phagocytic stimulation. Finally, IL-4 treatment also stimulated resting neutrophils to migrate toward zymosan-activated serum (ZAS) and human IL-5. The results demonstrate that IL-4 is a potent maturation factor for myelocytes to become neutrophils and that IL-4 can stimulate resting mature neutrophils.
Bober
L A
LA
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033.
Waters
T A
TA
Pugliese-Sivo
C C
CC
Sullivan
L M
LM
Narula
S K
SK
Grace
M J
MJ
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002460:Cell Line; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D018950:Lipopolysaccharide Receptors; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D011951:Receptors, Complement / Q000032:analysis
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018950:Lipopolysaccharide Receptors; D011951:Receptors, Complement; D015847:Interleukin-4