肺泡巨噬细胞在肺损伤机理中的作用

肺泡巨噬细胞在病理情况下有较强的组织损伤作用。它通过激活后释放多种生物活性物质而造成肺损伤。本文重点阐述肺泡巨噬细胞释放生物活性物质的种类及其在呼吸窘迫综合征、(ARDS)间质性肺疾病肺纤维化、肺气肿以及矽肺等肺损伤机理中的作用。     

矽肺患者肺泡巨噬细胞致纤维化作用的研究

本文研究矽肺患者全肺灌洗回收液(BALF)中,肺泡巨噬细胞(PAM)对肺成纤维细胞(FB)增殖的影响。4例矽肺病人的PAM培养2小时的上清液促FB增殖率为71.3％(FB培养第3天)～262％(FB培养第4天);2例非矽肺病人BALF中的PAM无明显促进作用。以上结果提示矽肺患者小气道和肺泡内存在着大量已吞噬矽尘并被激活的PAM,可能合成并释放出致纤维化因子,导致肺纤维化。     

肺泡巨噬细胞单层模型在生物药剂学中的应用

目的 建立体外肺泡巨噬细胞单层模型，用于研究药物在巨噬细胞的分布特征和相应机理，并可以用来预测药物（主要为治疗肺部炎症的抗生素），在体内分布到肺泡巨噬细胞的程度。方法 采用支气管肺泡洗净法（broncho-alveolar lavage,BAL）从大鼠肺部分离肺泡巨噬细胞，并进行纯化和体外培养，根据巨噬细胞的吸附特征通过少将法除去混杂的细胞，在95％air-5%CO2，37℃的细胞孵育箱下，进行肺泡巨噬细胞单层的体外培养，在此基础上，使用该模型初步考察了环丙沙星在肺泡巨噬细胞的分布。结果 丙沙星能够逆着细胞内外的浓度差向细胞内转运，使得细胞内外（I／E）药物的浓度比值为11。结论 肺泡巨噬细胞单层是有效的研究药物在体内分布到肺泡巨噬细胞的体外细胞模型。     

石英对大鼠肺泡巨噬细胞钙稳态的影响

石英对大鼠肺泡巨噬细胞钙稳态的影响刘保连，田琳，姚汝琳，李秋营石英如何引起肺泡巨噬细胞损伤的机制迄今为止并不完全清楚。其中钙稳态失调在石英致巨噬细胞损伤中的意义逐渐被人们重视［１，２］。为了进一步阐明石英损伤肺泡巨噬细胞的机制，研究了肺泡巨噬细胞在石...     

胆红素对烟雾损伤大鼠肺泡巨噬细胞的保护作用

目的:探讨胆红素对烟雾损伤所致肺泡巨噬细胞(AM)的保护作用,寻求防治肺气肿发生、发展的新途径。方法:将健康Wistar大鼠36只,随机分为正常对照组、肺气肿模型组和胆红素干预组。模型组及干预组采用自制大鼠实验性被动吸烟装置熏烟,连续6个月。干预组在熏烟前予以间接胆红素灌胃;模型组和对照组予以生理盐水灌胃。3组动物自由饮食饮水,6个月后处死动物,取材检测;病理形态学检查;采用支气管肺泡灌洗技术收集AM并纯化培养。观察细胞培养液上清中MDA与MO含量。结果:光镜下对照组大鼠肺组织肺泡分布较均匀;模型组大鼠肺组织肺泡普遍扩张,扩张的肺泡融合成较大的囊腔;胆红素干预组肺组织肺泡部分有扩张;模型组与对照比较MDA、MO含量升高(P<0.05);干预组与模型组比较MDA、NO含量降低(P<0.05)。结论:胆红素对于AM有一定的保护作用。     

肺泡巨噬细胞单层模型在生物药剂学中的应用

目的　 建立体外肺泡巨噬细胞单层模型 ,用于研究药物在巨噬细胞的分布特征和相应机理 ,并可以用来预测药物 (主要为治疗肺部炎症的抗生素 ) ,在体内分布到肺泡巨噬细胞的程度。 方法 　采用支气管肺泡洗净法(broncho alveolarlavage ,BAL)从大鼠肺部分离肺泡巨噬细胞 ,并进行纯化和体外培养。根据巨噬细胞的吸附特征通过洗净法除去混杂的细胞 ,在 95 %air 5 %CO2 ,37℃的细胞孵育箱下 ,进行肺泡巨噬细胞单层的体外培养。在此基础上 ,使用该模型初步考察了环丙沙星在肺泡巨噬细胞的分布。 结果 　环丙沙星能够逆着细胞内外的浓度差向细胞内转运 ,使得细胞内外 (I/E)药物的浓度比值为 11。 结论 　肺泡巨噬细胞单层是有效的研究药物在体内分布到肺泡巨噬细胞的体外细胞模型     

脂多糖对肺泡巨噬细胞自噬水平的影响

目的观察脂多糖(LPS)诱导肺泡巨噬细胞(NR8383)后,对细胞自噬水平的影响。方法 将体外培养的NR8383细胞分成LPS处理组和磷酸盐缓冲液(PBS)对照组,培养8h后,采用酶联免疫吸附法(ELISA)检测细胞培养上清液中肿瘤坏死因子-α(TNF-α)蛋白水平,自噬体检测:采用实时荧光定量聚合酶链反应(real-time PCR)检测细胞LC3 mRNA的转录水平、采用Western blot检测细胞LC3Ⅱ/LC3Ⅰ蛋白水平。结果 LPS处理组细胞培养上清液中TNF-α含量(pg/ml)较PBS对照组明显升高(639.20±43.49 vs 6.47±1.23,P<0.01),细胞LC3 mRNA转录水平较PBS对照组上调(3.4±0.36倍,P<0.01),细胞LC3Ⅱ/LC3Ⅰ较PBS对照组升高(1.03±0.15 vs 0.53±0.12,P<0.01)。结论 LPS刺激NR8383细胞后,细胞自噬体形成增多,其可能参与了NR8383肺泡巨噬细胞的炎症反应调控。     

外源性羟自由基对大鼠肺泡巨噬细胞脂质过氧化的影响

肺泡巨噬细胞(PAM)受损是矽肺发病的始动环节。石英粉尘可通过 OH·O_2~-等中介引起PAM 脂质过氧化(LPO),而 LPO 可通过多种途径导致膜损伤[1],所以 PAM 的 LPO 受到人们极大关注。由于石英粉尘的种类、研磨新鲜程度及     

Stimulation of Phagocytic Activity of Alveolar Macrophages Toward Artificial Microspheres by Infection with Mycobacteria

Purpose The purpose of this study is to know the effect of uptake of mycobacteria on the phagocytic activity of alveolar macrophage (Mφ) cells toward poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with the anti-tuberculosis agent rifampicin (RFP-PLGA MS). Materials and Methods Biological functions such as phagocytic activity toward PLGA MS loaded with fluorescent coumarin (cPLGA MS) and toward polystyrene latex MS (PSL MS), and generation of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were examined using alveolar Mφ cell NR8383 after they had phagocytosed Mycobacterium bovis Calmette-Guérin (BCG), heat-killed BCG (h-kBCG) or Escherichia coli. Results The ingestion of BCG, h-kBCG, and E. coli did not affect the viability of the Mφ cells within 2 days. The phagocytosis caused generation of TNF-α and NO, being more significant with E. coli than with both types of BCGs. The phagocytosis of both types of BCGs stimulated the phagocytic uptake of cPLGA and PSL MS’s, which took place prior to the generation of TNF-α or NO, but that of E. coli suppressed the uptake of both MS’s. Conclusion Mycobacterial infection stimulated the phagocytic uptake toward cPLGA MS. These results suggest that RFP-PLGA MS is favorable for overcoming tuberculosis.     

Phagolysosomal pH and Location of Particles in Alveolar Macrophages

Phagolysosomal pH and Location of Particles in Alveolar Macrophages.NYBERG, K., JOHANSSON, U., JOHANSSON, A., AND CAMNER, P. (1991).Fundam. Appl. Toxicol. 16, 393–400. Fluorescein-labeledsilica particles (FSP) were instilled into the tracheae of rabbits.Groups of four rabbits were killed after 24 hr, 1 week, 1 month,or 3 months and their lungs were lavaged. Phagolysosomal pHin the alveolar macrophages (AM) was measured using microscopefluorometry with FSP as a probe. Due to the marked decline ofthe fluorescence intensities from the FSP between 1 and 3 monthsafter instillation, it was not possible to measure pH at 3 months,but the values from 24 hr, 1 week, and 1 month were quite similar,with group means of 4.8 and 4.9, respectively. PhagolysosomalpH in AM which phagocytized the FSP in vitro showed values abouthalf a pH unit higher. AM from rabbits lavaged at 1 week hadmore lysosomes in contact with the FSP-containing phagolysosomesand a higher degree of vacuolization between the FSP and thephagolysosomal membrane than AM lavaged at 1 day. The locationof the FSP in the AM appeared to be similar in rabbits lavagedafter 1 week and 3 months. In histologic sections from the lungsthe large majority of the FSP were within cells at all timepoints.     

Shape Induced Inhibition of Phagocytosis of Polymer Particles

Purpose  To determine if particle shape can be engineered to inhibit phagocytosis of drug delivery particles by macrophages, which can be a significant barrier to successful therapeutic delivery. Methods  Non-spherical polystyrene particles were fabricated by stretching spherical particles embedded in a polymer film. A rat alveolar macrophage cell line was used as model macrophages. Phagocytosis of particles was assessed using time-lapse video microscopy and fluorescence microscopy. Results  We fabricated worm-like particles with very high aspect ratios (>20). This shape exhibits negligible phagocytosis compared to conventional spherical particles of equal volume. Reduced phagocytosis is a result of decreasing high curvature regions of the particle to two single points, the ends of the worm-like particles. Internalization is possible only at these points, while attachment anywhere along the length of the particles inhibits internalization due to the low curvature. Conclusions  Shape-induced inhibition of phagocytosis of drug delivery particles is possible by minimizing the size-normalized curvature of particles. We have created a high aspect ratio shape that exhibits negligible uptake by macrophages. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

肝靶向微粒给药系统的研究进展

目的对近年来微粒给药系统在肝靶向治疗的研究进展做一综述。方法根据国内外文献资料进行整理归纳。结果纳米粒、微球、脂质体及微乳等微粒系统具有被动靶向于肝的趋势,利用肝细胞表面某些受体则可特异性靶向于肝达到主动靶向作用。结论微粒给药系统在肝靶向治疗领域具有重要意义。     

基因药物肺部递送系统的研究进展

哮喘、肺气肿、囊性纤维化、肺部病毒感染和肺癌等多种肺部疾病严重影响人类的健康.基因治疗为肺部疾病治疗开辟了一个新的治疗途径.但因裸露的治疗基因易被降解、靶向能力差,因此需要安全有效的传递系统.本文将对基因药物在体内递送至肺部的给药屏障及可行性方法进行讨论.     

红霉素对哮喘患者肺泡巨噬细胞介质释放功能的影响

探讨红霉素的抗哮喘的气道炎症作用。方法：对２６例发作期过敏性哮喘患者肺泡巨噬细胞进行体外分别加红霉素、地塞米松，生理盐水培养，测定培养上清液中血栓素Ｂ２、肿瘤坏死因子－α、白介素－８水平。     

外泌体作为药物递送载体的研究进展

外泌体(exosomes)是一种由细胞分泌的纳米尺度(40~100 nm)的囊泡,在细胞间物质运输和信号交流中发挥重要作用。外泌体在大小和功能上与合成的纳米颗粒类似,但作为天然内源性转运载体,具有毒性低、无免疫原性、渗透性好等优势,故可能成为更有应用前景的药物递送载体。本文主要介绍了外泌体的基本性质和获得方法、载药方法及其作为纳米载体在小分子和生物大分子药物递送和靶向研究中的应用进展情况,并分析探讨了外泌体在载药和靶向递送方面的不足。     

煤尘对肺巨噬细胞体外毒性的研究

煤尘对肺巨噬细胞具有一定毒性，表现为细胞存活率降低，培养液中LDH和ACPI知性升高，并且存在剂量反应关系，经相关分析，八个煤矿煤尘的细胞毒性与各矿煤尘游离SiO2含量和采煤工尘肺发生率相关不显著，以煤尘离体细胞毒性来预测煤工尘肺发生率，应持慎重态度。     

Apoptotic and Inflammatory Effects Induced by Different Particles in Human Alveolar Macrophages

Pollutant particles induce apoptosis and inflammation, but the relationship between these two biological processes is not entirely clear. In this study, we compared the proapoptotic and proinflammatory effects of four particles: residual oil fly ash (ROFA), St. Louis particles SRM 1648 (SL), Chapel Hill PM10 (CHP), and Mount St. Helens dust (MSH). Human alveolar macrophages (AM) were incubated with these particles at 100 μg/ml. Cell death was assessed by annexin V (AV) expression, histone release, nuclear morphology, caspase 3-like activity and release of caspase 1 for apoptosis, and propidium iodide (PI) for necrosis, and inflammation was measured by interleukin (IL)-1β and IL-6. We found that particle effects on these cell death measurements varied, and ROFA affected most (four out of five) endpoints, including nuclear morphological changes. CHP and SL also caused necrosis. For cytokine release, the potency was CHP > SL > ROFA > MSH. The proapoptotic and proinflammatory effects induced by the whole particles were unaltered after the particles were washed with water. The water-soluble fraction was relatively inactive, as were individual soluble metals (V, Ni, Fe). ROFA-induced nuclear fragmentation was associated with upregulation and mitochondrial release of apoptosis-inducing factor (AIF), a caspase-independent chromatin condensation factor, and upregulation of DNase II, a lysosomal acid endonuclease. These results indicate that the potential for particles to induce apoptosis does not correlate with their proinflammatory properties, although active components for both processes reside in the water-insoluble core. Both apoptosis and inflammatory endpoints should be included when the toxicity of different pollutant particles is assessed.     

外泌体在胶质瘤治疗中的研究进展

胶质瘤是最常见的原发恶性脑肿瘤。传统化疗药物对胶质瘤靶向性差,且血脑屏障穿透性低,因而在胶质瘤治疗中的应用受到限制。外泌体作为新一代的递药载体,具有良好的生物相容性、稳定性和血脑屏障穿透性,近年来被广泛应用于脑部疾病的靶向递药研究,成果斐然。介绍了外泌体的结构和生物学特性,并对外泌体作为药物递送载体的脑靶向递送策略以及外泌体在胶质瘤治疗中的研究进展进行综述。