金诺芬对人中性粒细胞迁移的增强和抑制作用
Potentiation and inhibition of migration of human neutrophils by auranofin.
作者信息
Elferink J G, de Koster B M
机构信息
Department of Medical Biochemistry, University of Leiden, The Netherlands.
出版信息
Ann Rheum Dis. 1993 Aug;52(8):595-8. doi: 10.1136/ard.52.8.595.
OBJECTIVES
As auranofin resembles some neutrophil activating sulphur containing compounds, it was decided to investigate whether it had activating effects on neutrophil migration in addition to the published inhibitory effects.
METHODS
The Boyden chamber assay was used to determine the migration velocity of human neutrophils. The difference between chemotaxis and chemokinesis was established with a chequerboard assay.
RESULTS
Low concentrations of auranofin stimulated human neutrophil migration; concentrations of auranofin higher than 1 mumol/l were inhibitory. Inhibitors of leukotriene formation, or of protein kinase C, had the same effect on auranofin induced potentiation of migration as on fMLP activated migration. Auranofin, at a concentration of 100 nmol/l, caused a transient increase in the cGMP level of neutrophils. The auranofin induced increase in migration was strongly inhibited by methylene blue and by LY83583, two inhibitors of cGMP accumulation.
CONCLUSIONS
The auranofin induced enhancement of migration is partly due to a chemokinetic effect, but mainly due to a chemotactic effect. The potentiating effect of auranofin on migration is not specifically due to the ability of the drug to inhibit protein kinase C activity or to generate leukotrienes. These results suggest that the enhancement of neutrophil migration by low levels of auranofin is related to the enhancement of cGMP levels in neutrophils.
目的
由于金诺芬类似于一些含硫的中性粒细胞激活化合物，因此决定除了已发表的抑制作用外，研究其对中性粒细胞迁移是否具有激活作用。
方法
采用博伊登小室试验来测定人中性粒细胞的迁移速度。通过棋盘分析确定趋化性和化学增活现象之间的差异。
结果
低浓度的金诺芬刺激人中性粒细胞迁移；金诺芬浓度高于1μmol/L时具有抑制作用。白三烯形成抑制剂或蛋白激酶C抑制剂对金诺芬诱导的迁移增强作用的影响与对fMLP激活的迁移的影响相同。浓度为100 nmol/L的金诺芬可导致中性粒细胞cGMP水平短暂升高。金诺芬诱导的迁移增加受到亚甲蓝和LY83583（两种cGMP积累抑制剂）的强烈抑制。
结论
金诺芬诱导的迁移增强部分归因于化学增活效应，但主要归因于趋化效应。金诺芬对迁移的增强作用并非特别归因于该药物抑制蛋白激酶C活性或生成白三烯的能力。这些结果表明，低水平的金诺芬增强中性粒细胞迁移与中性粒细胞中cGMP水平的升高有关。
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