Department of Dermatology, Faculty of Medicine, Suleyman Demirel University, 32260 Isparta, Turkey.
J Membr Biol. 2011 Dec;244(3):113-20. doi: 10.1007/s00232-011-9404-4. Epub 2011 Nov 4.
Behçet disease (BD) is a chronic, inflammatory, and multisystemic condition with an uncertain pathogenesis. One of the major immunologic findings in BD pathogenesis is increase in activity of neutrophil. An increase in the cytosolic free Ca²⁺Ca²⁺ concentration that induces Ca²⁺ signaling is an important step that participates in the neutrophil activation and reactive oxygen species production that leads to tissue damage in body cells. We aimed to investigate the effects of colchicine on oxidative stress and Ca²⁺ release in serum and neutrophil of BD patients with active and inactive periods. Twelve Behçet patients (6 active and 6 inactive) and 6 control subject were included in the study. Disease activity was considered by clinical findings. Serum and neutrophil samples were obtained from the patients and control subjects. Neutrophils from patients with active BD were divided into three subgroups and were incubated with colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem, respectively. Erythrocyte sedimentation rate, leucocytes counts, serum C-reactive protein, neutrophil, and serum lipid peroxidation and intracellular Ca²⁺ release levels were higher in active and inactive groups than in the control group, although their levels were lower in active group than in inactive group. However, neutrophil Ca²⁺ release levels were decreased in colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem groups group compared to active group. Serum glutathione, vitamin A, vitamin E, and β-carotene concentrations were lower in active and inactive groups than in the control group, although serum vitamin E and β-carotene concentrations were higher in the inactive group than in the active group. Neutrophil and serum glutathione peroxidase activity within the three groups did not change. In conclusion, we observed the importance of Ca²⁺ influx into the neutrophils and oxidative stress in the pathogenesis and activation of the patients with BD. Colchicine induced protective effects on oxidative stress by modulating Ca²⁺ influx in BD patients.
白塞病(BD)是一种慢性、炎症性、多系统疾病,其发病机制尚不确定。BD 发病机制中的主要免疫学发现之一是中性粒细胞活性增加。细胞浆游离 Ca²⁺浓度[Ca²⁺](i)的增加诱导 Ca²⁺信号转导是一个重要步骤,参与中性粒细胞的激活和活性氧物质的产生,导致体内细胞的组织损伤。我们旨在研究秋水仙碱对活动期和非活动期 BD 患者血清和中性粒细胞氧化应激和 Ca²⁺释放的影响。本研究纳入了 12 名白塞病患者(6 名活动期和 6 名非活动期)和 6 名对照组。通过临床发现来评估疾病活动度。从患者和对照组中获得血清和中性粒细胞样本。将活动期 BD 患者的中性粒细胞分为三组,分别用秋水仙碱、维拉帕米+地尔硫卓和秋水仙碱+维拉帕米+地尔硫卓孵育。与对照组相比,活动期和非活动期患者的红细胞沉降率、白细胞计数、血清 C 反应蛋白、中性粒细胞以及血清脂质过氧化和细胞内 Ca²⁺释放水平均较高,尽管活动期患者的上述水平较非活动期患者低。然而,与活动期组相比,秋水仙碱、维拉帕米+地尔硫卓和秋水仙碱+维拉帕米+地尔硫卓组的中性粒细胞 Ca²⁺释放水平降低。与对照组相比,活动期和非活动期患者的血清谷胱甘肽、维生素 A、维生素 E 和 β-胡萝卜素浓度较低,尽管非活动期患者的血清维生素 E 和 β-胡萝卜素浓度高于活动期患者。三组中性粒细胞和血清谷胱甘肽过氧化物酶活性无变化。综上所述,我们观察到 Ca²⁺内流和氧化应激在 BD 患者发病机制和激活中的重要性。秋水仙碱通过调节 BD 患者的 Ca²⁺内流对氧化应激产生保护作用。