OBJECTIVE To examine whether free (3-PD-5free) and/or liposomal (3-PD-5lipo) 6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin (3-PD-5) (1) modulate the effector functions of neutrophils from patients with rheumatoid arthritis under remission (i-RA) and with active disease (a-RA), in vitro; and (2) exert anti-inflammatory effect in a rat model of zymosan-induced acute joint inflammation. METHODS AND RESULTS Incorporation of 3-PD-5 into unilamellar liposomes of soya phosphatidylcholine and cholesterol was efficient (57.5 ± 7.9%) and yielded vesicles with low diameter (133.7 ± 18.4 nm), polydispersity index (0.39 ± 0.06), and zeta potential (- 1.22 ± 0.34 mV). 3-PD-5free (1 µM) and 3-PD-5lipo (3 µM) equally suppressed elastase release and reactive oxygen species generation in neutrophils from healthy subjects and i-RA and a-RA patients, stimulated with immune complexes. 3-PD-5free (20 µM) suppressed the release of neutrophil extracellular traps and chemotaxis in vitro, without clear signs of cytotoxicity. 3-PD-5lipo (1.5 mg/kg, i.p.) diminished joint edema and synovial infiltration of total leukocytes and neutrophils, without changing the synovial levels of TNF-α, IL-1β, and IL-6. CONCLUSION Altogether, the results reported herein indicate that 3-PD-5 is a promising modulator of the early stages of acute joint inflammation that can help to diminish not only excessive neutrophil infiltration in the synovia but also neutrophil activation and its outcomes in RA patients.

中文翻译：

---

3-苯基香豆素衍生物 6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin 在类风湿性关节炎患者和急性关节炎症大鼠中性粒细胞中的免疫调节作用。

目的检查游离 (3-PD-5free) 和/或脂质体 (3-PD-5lipo) 6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin (3-PD-5) ( 1) 在体外调节处于缓解期 (i-RA) 和患有活动性疾病 (a-RA) 的类风湿关节炎患者的中性粒细胞的效应功能；(2)在酵母聚糖诱导的急性关节炎症大鼠模型中发挥抗炎作用。方法和结果 将 3-PD-5 掺入到大豆磷脂酰胆碱和胆固醇的单层脂质体中是有效的 (57.5 ± 7.9%) 并产生了低直径 (133.7 ± 18.4 nm)、多分散指数 (0.39 ± 0.06) 和 zeta 电位的囊泡(- 1.22 ± 0.34 毫伏)。3-PD-5free (1 µM) 和 3-PD-5lipo (3 µM) 同样抑制健康受试者和 i-RA 和 a-RA 患者的中性粒细胞中弹性蛋白酶的释放和活性氧的产生，用免疫复合物刺激。3-PD-5free (20 µM) 在体外抑制中性粒细胞胞外陷阱的释放和趋化性，没有明显的细胞毒性迹象。3-PD-5lipo (1.5 mg/kg, ip) 减少了关节水肿和总白细胞和中性粒细胞的滑膜浸润，但不改变滑膜中 TNF-α、IL-1β 和 IL-6 的水平。结论 总之，本文报道的结果表明，3-PD-5 是一种很有前途的急性关节炎症早期调节剂，不仅有助于减少滑膜中过度的中性粒细胞浸润，而且有助于减少 RA 患者的中性粒细胞活化及其结果。) 减少关节水肿和总白细胞和中性粒细胞的滑膜浸润，而不改变 TNF-α、IL-1β 和 IL-6 的滑膜水平。结论 总之，本文报道的结果表明，3-PD-5 是一种很有前途的急性关节炎症早期调节剂，不仅有助于减少滑膜中过度的中性粒细胞浸润，而且有助于减少 RA 患者的中性粒细胞活化及其结果。) 减少关节水肿和总白细胞和中性粒细胞的滑膜浸润，而不改变 TNF-α、IL-1β 和 IL-6 的滑膜水平。结论 总之，本文报道的结果表明，3-PD-5 是一种很有前途的急性关节炎症早期调节剂，不仅有助于减少滑膜中过度的中性粒细胞浸润，而且有助于减少 RA 患者的中性粒细胞活化及其结果。