Wolach B, DeBoard J E, Coates T D, Baehner R L, Boxer L A
J Lab Clin Med. 1982 Jul;100(1):37-44.
The anti-inflammatory effects of gold compounds include suppression of PMN lysosomal enzyme release. Since lysosomal products can provoke PMN aggregation, we assessed the effect of two gold compounds, auranofin and GST, on suppressing aggregation, degranulation, and metabolic functions of the cells. Aggregation of 1 x 10(7) cytochalasin B-treated PMNs in response to 2 x 10(-7)M FMLP, as assessed by light scattering, was inhibited in a dose-dependent fashion by both drugs. Concentrations of auranofin ranging from 5 to 20 microM caused 30.8% to 89% inhibition, whereas 200 microM GST reduced aggregation by only 32%. FCS or BSA added to suspensions of normal PMNs considerably reduced the gold compound inhibitory effect on PMN aggregation. Cell viability assessed by dye exclusion and lactate dehydrogenase release was unaffected by the drugs. The suppressive activities of the drugs could not be removed by washing the PMNs. Correspondingly, the drugs suppressed lysosomal enzyme release induced by FMLP of PMNs rendered secretory with cytochalasin B. Concentrations of 20 microM auranofin and 200 microM GST resulted, respectively, in a 61.5% and 19.3% reduction of release of lysozyme, 61.7% and 27.1% reduction of beta-glucuronidase, 84.8% and 33.7%s reduction of myeloperoxidase, and 50.0% and 25.0% reduction of lactoferrin. Furthermore, auranofin inhibited 14C-1-glucose oxidation through the hexose monophosphate shunt in response to stimulation by either PMA or methylene blue. The in vivo studies suggested that auranofin could prevent neither neutropenia induced by zymosan-activated serum nor a corresponding rise in plasma lactoferrin levels. These findings suggest that the beneficial effect of gold compounds in rheumatoid arthritis are unlikely to be related to their ability to dampen PMN activation in vivo.
金化合物的抗炎作用包括抑制中性粒细胞溶酶体酶的释放。由于溶酶体产物可引发中性粒细胞聚集，我们评估了两种金化合物，即金诺芬和谷胱甘肽硫转移酶（GST）对抑制细胞聚集、脱颗粒及代谢功能的作用。通过光散射评估，在2×10⁻⁷M甲酰甲硫氨酸-亮氨酸-苯丙氨酸（FMLP）刺激下，1×10⁷经细胞松弛素B处理的中性粒细胞的聚集，受到两种药物剂量依赖性的抑制。金诺芬浓度在5至20微摩尔时，抑制率为30.8%至89%，而200微摩尔的GST仅使聚集减少32%。添加到正常中性粒细胞悬液中的胎牛血清（FCS）或牛血清白蛋白（BSA）显著降低了金化合物对中性粒细胞聚集的抑制作用。通过染料排除法和乳酸脱氢酶释放评估的细胞活力不受药物影响。通过洗涤中性粒细胞不能消除药物的抑制活性。相应地，药物抑制了用细胞松弛素B使具有分泌功能的中性粒细胞由FMLP诱导的溶酶体酶释放。20微摩尔金诺芬和200微摩尔GST的浓度分别导致溶菌酶释放减少61.5%和19.3%，β-葡萄糖醛酸酶减少61.7%和27.1%，髓过氧化物酶减少84.8%和33.7%，乳铁蛋白减少50.0%和25.0%。此外，金诺芬抑制了在佛波酯（PMA）或亚甲蓝刺激下通过磷酸己糖旁路的1⁴C-1-葡萄糖氧化。体内研究表明，金诺芬既不能预防由酵母聚糖激活血清诱导的中性粒细胞减少，也不能预防血浆乳铁蛋白水平相应升高。这些发现表明，金化合物在类风湿性关节炎中的有益作用不太可能与其在体内抑制中性粒细胞活化的能力有关。
