The Effects of Sarpogrelate on Superoxide Production by Human Neutrophils
The Effects of Sarpogrelate on Superoxide Production by Human Neutrophils
复制标题
沙格雷酯对人中性粒细胞产生超氧化物的影响
DOI：
10.1136/rapm-00115550-200003000-00009
复制
发表时间：
1999
影响因子：
5.1
通讯作者：
Y. Niwa
中科院分区：
文献类型：
--
作者：
K. Mikawa;H. Akamatsu;K. Nishina;M. Shiga;N. Maekawa;H. Obara;Y. Niwa
背景和目的中性粒细胞释放的超氧阴离子（O2−）在抗菌宿主防御系统和组织自体损伤中发挥重要作用。沙格雷酯是一种血清素受体拮抗剂，已成功用于治疗由动脉闭塞或缺血性血管疾病或微循环障碍引起的慢性疼痛。抑制 O2− 的产生可能不利于感染或有助于治疗这些疾病，其发病机制可能包括中性粒细胞活化。尽管可能存在临床问题，但尚无关于沙格雷酯对中性粒细胞功能影响的数据。本研究的目的是利用体外系统确定沙格雷酯是否会减少人类中性粒细胞产生 O2−。此外，我们还检查了细胞内钙离子 ([Ca2+]i) 浓度的变化，它是中性粒细胞产生 O2− 的机制之一。方法 在沙格雷酯不存在和存在（临床相关浓度：0.1×、10×和100×这些浓度）的情况下，测量人中性粒细胞或黄嘌呤-黄嘌呤氧化酶系统产生的O2 - 和[Ca2+]i。结果 沙格雷酯以剂量依赖性方式抑制中性粒细胞 O2− 的产生。临床相关浓度的药物抑制了这种中性粒细胞功能。相比之下，沙格雷酯未能抑制无细胞（黄嘌呤-黄嘌呤氧化酶）系统产生 O2−。沙格雷酯剂量依赖性地减弱趋化因子刺激的中性粒细胞中[Ca2+]i 的升高。结论 这些发现表明沙格雷酯（即使在临床相关浓度）能够抑制中性粒细胞产生 O2−。然而，该药物未能抑制过量的 O2 -（与中性粒细胞产生的水平相似）。该药物对中性粒细胞 [Ca2+]i 反应的抑制作用可能会导致中性粒细胞 O2 - 产生受损。需要使用体内系统进行进一步研究，以阐明沙格雷酯在临床环境中对 O2 - 的抑制作用。
Background and Objectives Superoxide anion (O2−) released from neutrophils plays an important role in antibacterial host defense system and tissue auto-injury. Sarpogrelate, a serotonin-receptor antagonist, has been successfully used for management of chronic pain caused by arterial occlusive or ischemic vascular diseases, or by microcirculation disturbances. Suppression of O2− generation may be detrimental to infection or contribute to the therapeutic approach to these diseases, the pathogenesis of which probably includes neutrophil activation. No data regarding the effects of sarpogrelate on neutrophil functions are available despite the possible clinical concern. The purpose of this study was to determine whether sarpogrelate reduces O2− production by human neutrophils using an in vitro system. In addition, we examined changes in concentrations of the intracellular calcium ion ([Ca2+]i), which is responsible for one of the mechanisms of the neutrophils' O2− production. Methods The O2 − production by human neutrophils or the xanthine-xanthine oxidase system and [Ca2+]i were measured in the absence and the presence (at clinically relevant concentrations: 0.1×, 10×, and 100× these concentrations) of sarpogrelate. Results Sarpogrelate inhibited O2− production of neutrophils in a dose-dependent manner. The drug at a clinically relevant concentration suppressed this neutrophil function. In contrast, sarpogrelate failed to inhibit O2− generation by the cell-free (xanthine-xanthine oxidase) system. Elevation of [Ca2+]i in neutrophils stimulated by a chemotactic factor was dose-dependently attenuated with sarpogrelate. Conclusions These findings suggest that sarpogrelate (even at clinically relevant concentrations) is able to inhibit O2− production by neutrophils. However, the drug failed to quench an excessive amount of O2 − (similar to the level produced by neutrophils). There is a possibility that the inhibitory effect of the drug on [Ca2+]i response in neutrophils may contribute to impairment of the neutrophils' O2 − production. Further studies using in vivo systems are required to elucidate the inhibitory effects of sarpogrelate on O2 − in clinical settings.
DOI：
--
发表时间：
1996-05
期刊：
New horizons
影响因子：
--
作者：
D. Partrick;F. Moore;Ernest E. Moore;C. Barnett;C. Silliman
通讯作者：
D. Partrick;F. Moore;Ernest E. Moore;C. Barnett;C. Silliman