Abstract

Context

Effects of liposomal particles on immune function have not been adequately investigated. Earlier reports indicate that intravenous injection of rats with pegylated liposomes comprising chemically defined specific lipids produces myeloid derived suppressor-cell (MDSC)-like cells in the spleen.

Objectives

After liposome injection, we sought a cell surface marker expressed specifically on splenic macrophages. Then we assessed the immunosuppressive activity of macrophages positive for the marker. Furthermore, we investigated whether immunosuppression induction is an immunopharmacological action specific to this pegylated liposome, or not.

Materials and Methods

After using a microarray system to screen genes enhanced by this liposome, we evaluated cell surface expression of gene products using flow cytometry. Liposomes of several kinds, each comprising one type of phospholipid, were prepared and evaluated for their ability to induce T-cell suppression.

Results

Microarray analysis indicated enhanced B7-H3 expression. Flow cytometry revealed that the B7-H3 molecule was expressed on splenic macrophages after liposome injection. B7-H3⁺ macrophages were positive for iNOS. Removing B7-H3⁺ cells restored T-cell proliferation. Similarly to this liposome, various liposomes with different long chain fatty acids induced T-cell suppression when accumulated in the spleen.

Conclusions

Immunosuppressive cells induced by this pegylated liposome closely resemble MDSCs, especially B7-H3⁺ MDSCs. Immunosuppression induction is not a phenomenon specific to this liposome. Accumulation of long chain fatty acid in macrophages by internalization of liposomal nanoparticles might be related to macrophage acquisition of immunosuppressive activity in vivo.

中文翻译：

---

长链脂肪酸对髓样抑制细胞（MDSC）样细胞的诱导作用–脂质囊泡（脂质体）对MDSC的诱导

摘要

语境

脂质体颗粒对免疫功能的影响尚未得到充分研究。较早的报道表明，向大鼠静脉内注射含有化学成分确定的特定脂质的聚乙二醇化脂质体会在脾脏中产生髓样来源的抑制细胞（MDSC）样细胞。

目标

脂质体注射后，我们寻求在脾脏巨噬细胞上特异性表达的细胞表面标记。然后，我们评估了标记物阳性的巨噬细胞的免疫抑制活性。此外，我们研究了免疫抑制诱导是否是这种聚乙二醇化脂质体特有的免疫药理作用。

材料和方法

使用微阵列系统筛选该脂质体增强的基因后，我们使用流式细胞仪评估了基因产物的细胞表面表达。制备了几种脂质体，每种都包含一种类型的磷脂，并评估了它们诱导T细胞抑制的能力。

结果

微阵列分析表明B7-H3表达增强。流式细胞仪显示，脂质体注射后，B7-H3分子在脾巨噬细胞上表达。B7-H3 ⁺巨噬细胞对iNOS呈阳性。去除B7-H3 ⁺细胞可恢复T细胞增殖。类似于该脂质体，当具有不同长链脂肪酸的各种脂质体积聚在脾脏中时，它们会诱导T细胞抑制。

结论

该聚乙二醇化脂质体诱导的免疫抑制细胞与MDSC非常相似，尤其是B7-H3 ⁺ MDSC。免疫抑制诱导不是该脂质体特有的现象。脂质体纳米粒内在化在巨噬细胞中积累长链脂肪酸可能与体内巨噬细胞获得免疫抑制活性有关。