Bober L A, Waters T A, Pugliese-Sivo C C, Sullivan L M, Narula S K, Grace M J
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033.
Clin Exp Immunol. 1995 Jan;99(1):129-36. doi: 10.1111/j.1365-2249.1995.tb03483.x.
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.
白细胞介素-4是一种由辅助性T细胞产生的细胞因子，对骨髓单核细胞的成熟和激活有影响。我们利用HL-60细胞系研究了白细胞介素-4对嗜中性粒细胞成熟的影响，发现它对该细胞系的成熟和激活有深远影响。用重组人白细胞介素-4（0.15至15.0纳克/毫升）处理HL-60细胞，可使氯乙酸酯酶活性染色呈阳性的HL-60细胞百分比发生变化（表明向嗜中性粒细胞系分化）。白细胞介素-4增加了嗜中性粒细胞系抗原WEM G11、补体受体CR3（CD11b）和CR1（CD35）的表面表达，但单核细胞分化抗原CD14的表达未增加。经白细胞介素-4处理的HL-60细胞表现出增强的Fc和补体介导的吞噬能力以及增加的磷酸己糖旁路活性。此外，白细胞介素-4能够维持用二甲基亚砜预处理24小时的HL-60细胞的嗜中性粒细胞成熟。为了研究白细胞介素-4对成熟嗜中性粒细胞的影响，我们研究了新鲜分离并静置的人外周血嗜中性粒细胞。在没有其他刺激的情况下，白细胞介素-4可诱导嗜中性粒细胞产生显著升高的吞噬反应。该反应具有特异性，因为用抗人白细胞介素-4处理可消除吞噬刺激。最后，白细胞介素-4处理还刺激静置的嗜中性粒细胞向酵母聚糖激活的血清（ZAS）和人白细胞介素-5迁移。结果表明，白细胞介素-4是一种使髓细胞分化为嗜中性粒细胞的有效成熟因子，并且白细胞介素-4可以刺激静置的成熟嗜中性粒细胞。
