Cationic liposomes evoke proinflammatory mediator release and neutrophil extracellular traps (NETs) toward human neutrophils
Cationic liposomes evoke proinflammatory mediator release and neutrophil extracellular traps (NETs) toward human neutrophils
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DOI：
10.1016/j.colsurfb.2015.02.022
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发表时间：
2015-04-01
影响因子：
5.8
通讯作者：
Fang, Jia-You
中科院分区：
文献类型：
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作者：
Hwang, Tsong-Long;Hsu, Ching-Yun;Fang, Jia-You
阳离子脂质体广泛用作用于治疗和诊断目的的纳米载体。脂质体的阳离子组分可诱导炎症反应。本研究考察了阳离子脂质体对人中性粒细胞活化的影响。将十六烷基三甲基溴化铵（CTAB）或大豆乙基吗啉乙基硫酸盐（SME）作为阳离子添加剂掺入脂质体中。研究了脂质体的细胞毒性及其对促炎介质、细胞内钙和中性粒细胞胞外陷阱（NETS）的诱导。脂质体与质膜的相互作用触发了中性粒细胞的刺激。CTAB脂质体在所有测试浓度下诱导乳酸脱氢酶（LDH）完全泄漏，而SME脂质体以浓度依赖性方式释放LDH。与SME脂质体相比，CTAB脂质体被证明能更有效地激活中性粒细胞，如超氧阴离子和弹性蛋白酶水平增加所示。CFAS脂质体处理后，钙内流增加9倍。与未处理的对照相比，SME脂质体没有改变这种流入。扫描电子显微镜（SEM）和免疫荧光图像表明与阳离子脂质体处理后的NET的存在。在CAB脂质体处理后，NET可以在几分钟内快速形成。与此结果相反，SME脂质体在4 h内缓慢且逐渐增加NET形成。根据此处提供的数据，重要的是要考虑阳离子脂质体在体内给药期间的毒性。这是第一份提供阳离子脂质体诱导NET产生证据的报告。(c)2015 Elsevier B.V.版权所有。
Cationic liposomes are widely used as nanocarriers for therapeutic and diagnostic purposes. The cationic components of liposomes can induce inflammatory responses. This study examined the effect of cationic liposomes on human neutrophil activation. Cetyltrimethylammonium bromide (CTAB) or soyaethyl morpholinium ethosulfate (SME) was incorporated into liposomes as the cationic additive. The liposomes' cytotoxicity and their induction of proinflammatory mediators, intracellular calcium, and neutrophil extracellular traps (NETS) were investigated. The interaction of the liposomes with the plasma membrane triggered the stimulation of neutrophils. CTAB liposomes induced complete leakage of lactate dehydrogenase (LDH) at all concentrations tested, whereas SME liposomes released LDH in a concentration-dependent manner. CTAB liposomes proved to more effectively activate neutrophils compared with SME liposomes, as indicated by increased superoxide anion and elastase levels. Calcium influx increased 9-fold after treatment with CFAS liposomes. This influx was not changed by SME liposomes compared with the untreated control. Scanning electron microscopy (SEM) and immunofluorescence images indicated the presence of NETs after treatment with cationic liposomes. NETs could be quickly formed, within minutes, after CAB liposomal treatment. In contrast to this result, NET formation was slowly and gradually increased by SME liposomes, within 4 h. Based on the data presented here, it is important to consider the toxicity of cationic liposomes during administration in the body. This is the first report providing evidence of NET production induced by cationic liposomes. (c) 2015 Elsevier B.V. All rights reserved.