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他汀类药物增强血小板对 的抗菌作用。

Statins potentiate the antibacterial effect of platelets on .

机构信息

IHU Méditerranée Infection, Aix Marseille University, IRD, APHM, MEPHI, Marseille, France.

IHU Méditerranée Infection, Aix Marseille University, IRD, SSA, APHM, VITROME, Marseille, France.

出版信息

Platelets. 2021 Jul 4;32(5):671-676. doi: 10.1080/09537104.2020.1792434. Epub 2020 Jul 14.

Abstract

Platelets have largely demonstrated their implication in anti-infectious immunity. This effect is ensured by the secreted molecules stored mostly in platelet alpha granules. Previous studies have reported that showed sensitivity to this antibacterial effect of platelets. Statins, for their part, have shown a modulating effect on platelet activation. Furthermore, several studies have reported a protective effect of statins in staphylococcal endocarditis. The aim of this study was to investigate the influence of statins on the antibacterial effect of washed platelets. Blood samples were collected from healthy donors (n = 35). PRP was prepared according to the ISTH recommendation. Bacteria were incubated for four hours with untreated-washed platelets, or rather treated by statins and/or GPIIbIIIa antagonists. In order to evaluate the antibacterial effect, the platelet-bacteria mix was spread on the blood agar to count the number of colonies after 18 hours of incubation. Measurement of CD 41 and CD62P expression by flow cytometry was performed to evaluate the effect of statin on bacterial-induced platelet activation. Statins have shown a potentiation of the antibacterial effect of washed platelets ( < .01 for Atorvastatin and Rosuvastatin and < .001 for Fluvastatin untreated washed platelets condition). This effect of statins was dose-dependent and was more significant at 20 μM. The addition of Fluvastatin to platelet-bacterial mix significantly increased the expression of platelet CD41 and CD62P ( < .05 and < .01 vs resting washed platelets, respectively). Tirofiban, GPIIbIIIa antagonist, reversed the antibacterial effect of washed platelets and suppressed the potentiating effect of statins. Our study demonstrated that statins potentiate the anti-staphylococcal effect of washed platelets. This result may explain the beneficial effect of statins on infective endocarditis. Further studies are therefore required to explain this effect at the molecular level and to assess its impact .

摘要

血小板在抗感染免疫中发挥了重要作用。这种作用是通过储存在血小板α颗粒中的分泌分子来实现的。先前的研究表明,血小板对这种抗菌作用敏感。他汀类药物则对血小板激活具有调节作用。此外,多项研究报告称,他汀类药物对金黄色葡萄球菌心内膜炎具有保护作用。本研究旨在探讨他汀类药物对洗涤血小板抗菌作用的影响。从健康供体中采集血液样本(n=35)。根据 ISTH 建议制备 PRP。将细菌与未经处理的洗涤血小板孵育 4 小时,或者用他汀类药物和/或 GPIIbIIIa 拮抗剂处理。为了评估抗菌作用,将血小板-细菌混合物涂在血琼脂上,孵育 18 小时后计数菌落数。通过流式细胞术测量 CD41 和 CD62P 的表达,以评估他汀类药物对细菌诱导的血小板激活的影响。他汀类药物增强了洗涤血小板的抗菌作用(阿托伐他汀和瑞舒伐他汀<0.01,未处理的洗涤血小板条件下氟伐他汀<0.001)。这种他汀类药物的作用呈剂量依赖性,在 20 μM 时更为显著。在血小板-细菌混合物中添加氟伐他汀显著增加了血小板 CD41 和 CD62P 的表达(与静息洗涤血小板相比,分别为<0.05 和<0.01)。血小板 GPIIbIIIa 拮抗剂替罗非班逆转了洗涤血小板的抗菌作用,并抑制了他汀类药物的增强作用。本研究表明,他汀类药物增强了洗涤血小板对金黄色葡萄球菌的抗菌作用。这一结果可能解释了他汀类药物对感染性心内膜炎有益的作用。因此,需要进一步研究来解释这种作用的分子机制,并评估其影响。

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