Borish L, O'Reilly D, Klempner M S, Rocklin R E
J Immunol. 1986 Sep 15;137(6):1897-903.
The ability of purified (80,000-fold) human leukocyte inhibitory factor (LIF) to modulate several formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe)-induced neutrophil functions was evaluated. Although not affecting directed migration itself, at low concentrations (1/2 to 2 U/ml), LIF was demonstrated to potentiate chemotaxis induced by f-met-leu-phe (40.3% +/- 8.1) and to reduce the concentration of f-met-leu-phe necessary for maximal chemotaxis (10(-8) to 10(-9) M). Similarly, LIF did not directly induce the respiratory burst, but potentiated both superoxide generation (151.6% +/- 77) and hydrogen peroxide production (54.9% +/- 15.5) in the presence of f-met-leu-phe (10(-7) M). LIF was also shown to induce degranulation of neutrophil-specific granules in a dose-dependent manner. Neutrophil-specific granules have been shown to contain an intracellular pool of receptors for f-met-leu-phe, and on degranulation provide the surface membrane with a fresh source of receptors. Our data suggested that LIF potentiation of neutrophil stimulation by f-met-leu-phe might be mediated, at least in part, by increasing the number of available membrane receptors as a result of its ability to induce degranulation. Radioligand receptor analysis using f-met-leu-[3H] phe was performed, and LIF was shown to mediate an increase in receptors for f-met-leu-phe from an average of 18,600 on untreated cells to 27,000 after pretreatment with LIF. This increase in receptors could "sensitize" the neutrophils for f-met-leu-phe and possibly explain the potentiation of neutrophil stimulation observed in the presence of the ligand. LIF was also found to have a more generalized effect on the transduction of neutrophil activation stimuli, mediating a 35.8% increase in superoxide production after exposure to calcium ionophore. The data do not permit a determination as to whether the increase in receptor number is responsible for the potentiation of f-met-leu-phe-mediated function, or whether this occurs secondary to the more generalized effect on neutrophil stimulation transduction.
评估了纯化的（80000倍）人白细胞抑制因子（LIF）调节几种甲酰甲硫氨酰亮氨酰苯丙氨酸（f-met-leu-phe）诱导的中性粒细胞功能的能力。虽然LIF本身不影响定向迁移，但在低浓度（1/2至2 U/ml）时，LIF被证明可增强f-met-leu-phe诱导的趋化作用（40.3%±8.1），并降低最大趋化作用所需的f-met-leu-phe浓度（从10^-8降至至10^-9 M）。同样，LIF不会直接诱导呼吸爆发，但在存在f-met-leu-phe（10^-7 M）的情况下，可增强超氧化物生成（151.6%±77）和过氧化氢产生（54.9%±15.5）。LIF还被证明以剂量依赖的方式诱导中性粒细胞特异性颗粒的脱颗粒。中性粒细胞特异性颗粒已被证明含有f-met-leu-phe的细胞内受体池，脱颗粒时为表面膜提供新的受体来源。我们的数据表明，LIF对f-met-leu-phe刺激中性粒细胞的增强作用可能至少部分是由于其诱导脱颗粒的能力增加了可用膜受体的数量。使用f-met-leu-[3H]phe进行了放射性配体受体分析，结果显示LIF可介导f-met-leu-phe受体从未处理细胞上的平均18600个增加到LIF预处理后的27000个。受体的这种增加可使中性粒细胞对f-met-leu-phe“敏感”，并可能解释在配体存在下观察到的中性粒细胞刺激增强现象。还发现LIF对中性粒细胞激活刺激的转导有更广泛的影响，在暴露于钙离子载体后介导超氧化物产生增加35.8%。这些数据无法确定受体数量的增加是否是f-met-leu-phe介导功能增强的原因，或者这是否是对中性粒细胞刺激转导更广泛影响的继发结果。
