目的 探索α-突触核蛋白（α-Syn）干预对人单核细胞白血病细胞系（THP-1）巨噬细胞源性泡沫细胞的影响。方法 通过佛波酯（PMA）和氧化型低密度脂蛋白（ox-LDL）构建THP-1巨噬细胞源性泡沫细胞模型,使用不同浓度（33、66、100、133 nmol/L）α-Syn处理泡沫细胞,随后检测细胞胆固醇含量和炎症因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）及白细胞介素-8（IL-8）的mRNA表达以及核因子κB（NF-κB）和凝集素样氧化低密度脂蛋白受体-1（LOX-1）的蛋白表达变化。结果 高剂量（100和133 nmol/L）α-Syn处理可以减少THP-1巨噬细胞源性泡沫细胞内胆固醇的含量（P<0.05）,并且减少IL-1β、IL-6和IL-8的mRNA表达（P<0.05）。进一步发现（100 nmol/L和133 nmol/L）α-Syn可以降低THP-1巨噬细胞源性泡沫细胞p-NF-κB和LOX-1的蛋白表达（P<0.05）。结论 α-Syn可以降低THP-1源性巨噬细胞泡沫细胞胆固醇蓄积和炎症反应,可能是通过下调p-NF-κB和LOX-1蛋白表达。

      Objective To explore the effects of α-synuclein（α-Syn）intervention on human monocytic leukemia cell（THP-1）macrophage-derived foam cells．Methods The THP-1 macrophage-derived foam cell model was constructed by phorbol 12-myristate 13-acetate（PMA）and oxidized low-density lipoprotein（ox-LDL）．Foam cells were treated with different concentrations（33, 66, 100, and 133 nmol/L）of α-Syn, and the cellular cholesterol contents, as well as the mRNA expression of IL-1β、IL-6 and IL-8 were detected．Subsequently,alternation in protein expression of NF-κB and LOX-1 was measured．Results High-dose（100 and 133nmol/L）α-Syn treatment significantly reduced the levels of intracellular cholesterol in THP-1-derived macrophage foam cells（P<0.05）and decreased the mRNA expression of IL-1β、IL-6 and IL-8（P<0.05）．It was further found that（100 nmol/L and 133 nmol/L）α-Syn decreased the protein expression of p-NF-κB and LOX-1 in THP-1 macrophage-derived foam cells（P<0.05）．Conclusions The results of the present study suggest that α-Syn reduces cholesterol accumulation and inflammatory response in THP-1-derived macrophage foam cells, possibly by down-regulating p-NF-κB and LOX-1 protein expression．

肿瘤相关巨噬细胞（TAMs）是肿瘤微环境中最丰富的免疫细胞之一,M2-TAMs在肿瘤发生、发展、转移和治疗过程中发挥重要作用,被认为是肿瘤治疗中的重要靶点。已有的研究表明,通过将促肿瘤的M2-TAMs重编程为促炎的M1-TAMs可实现抑制肿瘤生长和转移。本综述在介绍TAMs与肿瘤治疗相关背景的基础上,重点关注纳米药物重编程TAMs增强抗肿瘤的研究进展。本文将从TAMs靶向递送各种活性物质进行重编程TAMs和纳米药物介导的异常肿瘤微环境调节的间接重编程TAMs两种方式,综述近年来基于纳米药物递送系统的调控策略及典型例子。

Tumor associated macrophages（TAMs）is one of the most abundant immune cells in the tumor microenvironment．M2-TAMs play an important role in tumor genesis,progression,metastasis and treatment,and is additionally a very important target in tumor therapy．Previous studies have shown that inhibition of tumor growth and metastasis can be achieved by reprogramming M2-TAMs to M1-TAMs．On the basis,this review focuses on the analysis progress of nano-drug reprogramming TAMs to boost anti-tumor．In this paper,we reviewed two methods of reprogramming TAMs for targeted delivery of various active substances and indirect reprogramming TAMs for abnormal tumor microenvironment regulation mediated by nanomedicine．The regulatory strategies and typical samples of nanomedicine delivery systems in recent years were summarized.

目的 探讨磷酸二酯酶4抑制剂对人肺泡巨噬细胞(AM)吞噬非生物性颗粒及革兰阳性菌、阴性菌能力的影响。方法 使用Ficolll-Hypaque密度梯度法将外周血单核细胞分离的静脉血,在含有2 ng/m GM-CSF的培养液中经12天诱导培养成AM替代细胞模型—单核细胞源性巨噬细胞(MDM)。用酶标仪检测MDM经磷酸二酯酶4抑制剂Rolipram预处理过夜(16~18 h)后吞噬荧光标记的非生物颗粒Beads和热灭活的流感嗜血杆菌(H.influenzae)、金黄色葡萄球菌(S.aureus)量的改变,另使用MTT法检测细胞活性。结果 成功建立的MDM细胞模型对Beads和细菌的吞噬呈时效关。Rolipram在实验浓度(10^~8~10^-5 M)下对MDM吞噬Beads、H.influenzae和S.aureus能力无明显促进或抑制作用,也不影响MDM的活性。结论 磷酸二酯酶4抑制剂不会因升高巨噬细胞内cAMP水平而影响其吞噬非生物颗粒和细菌的能力。

Objective To investigate the influence of phosphodiesterases 4 inhibitor on the phagocytosis of non-biological particles and gram-positive bacteria, gram-negative bacteria by human alveolar macrophages. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood from 12 healthy volunteers using Ficoll-Hypaque density gradients. Monocytes were incubated with media containing 2 ng/ml GM-CSF for 12d to allow full differentiation into macrophage (MDM), a functionally equivalent model of human AM. MDM were pretreated with Rolipram overnight (16-18h),phagocytosis of fluorescent labeled beads and H.influenzae,S.aureus by MDM was measured using a fluostar optima fluorimeter. Cell viability was assay with MTT. Results MDM phagocytosis of beads and bacteria was a time-dependant process. Rolipram in the concentration of 10^-8-10^-5M didn't inhibit or promote phagocytosis of beads and bacteria by MDM, and didn't affect the cell viability. Conclusion Phosphodiesterases 4 inhibitor would not affect the human macrophage phagocytic capacity of non-biological particles and bacteria associated with enhanced intracellular cAMP level.