Swain S D, Bunger P L, Sipes K M, Nelson L K, Jutila K L, Boylan S M, Quinn M T
Department of Veterinary Molecular Biology, Montana State University, Bozeman 59717, USA.
J Leukoc Biol. 1998 Dec;64(6):817-27. doi: 10.1002/jlb.64.6.817.
We characterized the dose response of bovine neutrophils to platelet-activating factor (PAF) with respect to the following functions: calcium flux and membrane potential changes, actin polymerization, degranulation, and the production and/or priming of the oxidative burst. PAF at very low concentrations (10(-10) and 10(-9) M) caused changes in intracellular calcium and membrane potential in bovine neutrophils, whereas moderate PAF concentrations (> or = 10(-7) M) resulted in increased actin polymerization. Degranulation responses to PAF were more complex: low concentrations (10(-9) M) caused secretory granule degranulation, moderate doses (> or = 10(-7) M) caused specific granule degranulation, whereas azurophil degranulation only occurred at high (10(-5) M) PAF concentrations. Treatment of bovine neutrophils with PAF at concentrations > or = 10(-7) M also caused up-regulation of the adhesion molecules Mac-l and L-selectin. PAF stimulation resulted in a very weak [compared to phorbol myristate acetate (PMA)] oxidative burst in bovine neutrophils, and only at high (10(-6) M) concentrations. Unlike human neutrophils, bovine neutrophils were poorly primed by PAF treatment. Only high concentrations of PAF (10(-5) M) caused an increased rate of PMA-stimulated superoxide production, although lower doses of PAF did reduce the lag time preceding the PMA-induced oxidative burst. The overall pattern that can be inferred is that lower concentrations of PAF promote neutrophil sensitivity and interaction by selective degranulation, up-regulation of adhesion molecules, and increased actin polymerization. In contrast, higher PAF concentrations can promote, albeit weakly, more direct bactericidal responses, such as the release of reactive oxygen species and granule enzymes. The ability of PAF to modulate a graded response in bovine neutrophils would allow the cell to respond proportionally to the severity of a stimulus.
我们针对以下功能对牛中性粒细胞对血小板活化因子（PAF）的剂量反应进行了表征：钙通量和膜电位变化、肌动蛋白聚合、脱颗粒以及氧化爆发的产生和/或启动。极低浓度（10^(-10)和10^(-9) M）的PAF会引起牛中性粒细胞内钙和膜电位的变化，而中等浓度的PAF（≥10^(-7) M）会导致肌动蛋白聚合增加。对PAF的脱颗粒反应更为复杂：低浓度（10^(-9) M）会导致分泌颗粒脱颗粒，中等剂量（≥10^(-7) M）会导致特异性颗粒脱颗粒，而嗜天青颗粒脱颗粒仅在高浓度（10^(-5) M）的PAF时发生。用≥10^(-7) M浓度的PAF处理牛中性粒细胞也会导致黏附分子Mac-1和L-选择素的上调。PAF刺激在牛中性粒细胞中导致非常微弱的（与佛波酯肉豆蔻酸酯乙酸盐（PMA）相比）氧化爆发，且仅在高浓度（10^(-6) M）时出现。与人类中性粒细胞不同，PAF处理对牛中性粒细胞的启动作用较弱。只有高浓度的PAF（10^(-5) M）会导致PMA刺激的超氧化物产生速率增加，尽管较低剂量的PAF确实会缩短PMA诱导的氧化爆发之前的延迟时间。可以推断出的总体模式是，较低浓度的PAF通过选择性脱颗粒、黏附分子上调和肌动蛋白聚合增加来促进中性粒细胞的敏感性和相互作用。相比之下，较高浓度的PAF尽管作用较弱，但可以促进更直接的杀菌反应，如活性氧物质和颗粒酶的释放。PAF调节牛中性粒细胞分级反应的能力将使细胞能够根据刺激的严重程度做出成比例的反应。
