Papillary adenoma of type II pneumocytes might have malignant potential

Papillary adenoma of type II pneumocytes is a rare tumour. It is considered to be a benign neoplasm and is derived from immature cells in the bronchioloalveolar epithelium, however, its biological nature has not been elucidated. We report a case of an adenomatous tumour; a papillary adenoma of type II pneumocytes, which we regard as possessing malignant potential. Light microscopically, as well circumscribed, papillary tumour of predominantly cuboidal cells resembling type II pneumocytes was found, but Clara type and ciliated cells were also present. Immunohistochemically, the tumour cells reacted positively with antibodies to surfactant apoproteins (A, B), carcinoembryonic antigen, cytochrome P-450 1A1-2 and 2B1-2. Ultrastructurally, many osmiophilic lamellar bodies and electron-dense granules were demonstrated. Semi-serial sections revealed signs of transbronchial dissemination and vascular invasion. Morphometry using 12-dimensional cluster analysis disclosed features of the tumour cells which resembled those of pneumocyte type II adenocarcinoma. These findings suggest that the present case has some malignant characteristics and originates from immature bronchiolar or alveolar cells, with a potential to develop into both type II pneumocyte and Clara cell type adenocarcinomas.     

Pneumocyte Apoptosis Induction during Cardiopulmonary Bypass: Effective Prevention by Radical Scavenging Using N-Acetylcysteine

Cardiopulmonary bypass (CPB) and cardioplegic arrest are associated with pulmonary dysfunction. We sought to investigate whether pulmonary ischemia/reperfusion during standard CPB and cardioplegic arrest is associated with reactive oxygen species (ROS)-mediated pulmonary tissue injury and pneumocyte apoptosis induction, and whether ROS scavenging using N-acetylcysteine (NAC) attenuates these alterations. Twelve pigs (41 ± 8 kg) were randomized to receive either NAC (100 mg/kg prior to CPB; n = 7) or placebo (n = 5) and subjected to CPB and 60 min of cold (4°C) crystalloid cardioplegic arrest. We collected lung biopsies prior to CPB, at 60 min CPB, as well as at 30, 60, and 120 min post CPB. Lung specimens were immunocytochemically stained against nitrotyrosine, 8-isoprostaglandin-F₂α, and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) as indicators for ROS-mediated tissue injury and active caspase-3, an apoptosis signal pathway key enzyme. Oxidative stress markers were judged using a scale from 1 to 4 (low to intensive staining), and caspase-3-positive pneumocytes were counted per view field. In placebo, the number of caspase-3-positive pneumocytes significantly increased over time to reach a maximum at 120 min post CPB (p =. 03 vs baseline). NAC significantly prevented caspase-3 activation in pneumocytes (p =. 001 vs Placebo). Pneumocyte nitrotyrosine and 8-OH-dG staining significantly increased over time (p =. 003) in the placebo group, but decreased in the NAC group (p =. 004). In both groups staining for 8-isoprostaglandin-F₂α showed no significant changes. This yields the conclusion that standard CPB and cardioplegic arrest initiate ROS-mediated tissue injury and apoptosis in pneumocytes that can be reduced by NAC. Thus, ROS scavenging using NAC may represent a novel approach to minimize lung injury associated with CPB.     

铁路危险品货运站空气颗粒物诱导肺细胞氧化应激损伤

[目的 ]探讨铁路危险品货运站空气污染颗粒提取物诱导大鼠肺细胞氧化应激损伤作用的机制。 [方法 ]应用滤膜法采集铁路危险品货运站空气颗粒提取物。常规分离与原代培养大鼠肺Ⅱ型细胞 ,以N 乙酰半胱氨酸 (NAC)、维生素E(VitE)、维生素C(VitC)和甘露醇 (MT)等不同作用位点的抗氧化剂预处理 3 0min后 ,加入空气颗粒提取物染毒 2 4h。采用四氮甲基唑蓝比色法、溴乙锭荧光法检测肺细胞的生长情况和DNA交联的形成。 [结果 ]在 1 0 2～ 8 13mg/ml浓度范围内 ,铁路危险品货运站空气颗粒提取物对大鼠肺细胞有明显的细胞毒性和致DNA交联作用。加入NAC、VitE、VitC和MT可有效地减低铁路危险品货运站空气污染颗粒提取物所致的细胞毒性 ,VitE、VitC则具有减低铁路危险品货运站空气污染颗粒提取物所致的DNA损伤作用。 [结论 ]铁路危险品货运站空气污染颗粒提取物对大鼠肺细胞具有氧化应激作用 ,其可能途径是产生活性氧自由基、羟自由基或导致细胞过氧化等     

State of the lung surfactant in animals of different species

The activity of the lung surfactant in mice, rats, guinea pigs, hamsters, rabbits, and dogs was found to be within normal limits with variation of the coefficient of stability of the air bubbles between 0.84 and 0.93. Differences in the content of surfactant in animals of different species depend on the frequency, severity, and character of spontaneous pulmonary pathology. The data obtained can be used as the starting point for the study of the surfactant system of the lungs in various experimentally induced pathological states of the lung tissue.S. M. Kirov Military Medical Academy, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR I. S. Kolesnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 1, pp. 11–13, January, 1978.     

The effect of stone-wool on rat lungs and on the primary culture of rat alveolar macrophages and type II pneumocytes

The effect of stone-wool has been studied in both in vivo long term sequential and in vitro methods in male Sprague-Dawley rats. Stone-wool was administered by single intratracheal instillation and the lungs were examined after 1, 3 and 6 months of exposure by morphological methods. UICC crocidolite was applied as a positive control. In addition, the effects of both fibres were examined in primary cultures of alveolar macrophages (AM) and type II pneumocytes (T2) by morphological, biochemical and immunological methods. By the end of 6 months stone-wool induced moderate pulmonary interstitial inflammation and fibrosis without progression, whereas crocidolite induced progressive interstitial inflammation and fibrosis as a function of time. Although stone-wool inhibited phagocytosis, it did not induce serious membrane damage to the cells examined and did not destroy their ultrastructure. It significantly reduced the activity of Cu,Zn/superoxide dismutase (SOD) and alkaline phosphatase (AP) in alveolar macrophages and significantly decreased the activity of AP and gamma-glutamyl transpeptidase (GGT) in type II pneumocytes. Crocidolite, on the other hand, decreased the activity of all enzymes (glutathione peroxidase, GSH-Px; glutathione reductase, GSH-Rd) of glutathione metabolism as well as alkaline phosphatase in alveolar macrophages. It decreased the activity of all enzymes in type II pneumocytes, except for Cu,Zn/SOD. On exposure to stone-wool, the production of inflammatory proteins, macrophage chemoattractant protein-1 (MCP-1) and macrophage inhibitory protein-1alpha (MIP-1alpha) increased in both cultured cells but did not reach the level induced by crocidolite. Our results suggested that stone-wool is less toxic than crocidolite. Whether it is carcinogenic or not, is still an open question.     

Porcine Alveolar Epithelial Cells in Primary Culture: Morphological, Bioelectrical and Immunocytochemical Characterization

Purpose The purpose of this study was to establish a primary culture of porcine lung epithelial cells as an alternative to the currently existing cell cultures from other species, such as e.g., rat or human. Primary porcine lung epithelial cells were isolated, cultivated and analyzed at distinct time points after isolation.Materials and Methods The main part of the work focused on the morphology of the cells and the detection of alveolar epithelial cell markers by using electron microscopy, immunofluorescence microscopy and immunoblotting. Regarding a later use for in vitro pulmonary drug absorption studies the barrier properties of the cell monolayer were evaluated by monitoring bioelectrical parameters and by marker transport.Results Epithelial cells isolated from porcine lung grew to confluent monolayers with typical intercellular junctions within a few days. Maximum transepithelial resistance of about 2,000 Ωcm² was achieved and demonstrated the formation of a tight epithelial barrier. Permeability data of sodium fluorescein recommended a minimal transepithelial resistance of 600 Ωcm² for transport studies. The cell population changed from a heterogeneous morphology and marker distribution (caveolin-1, pro-SP-C, surface sugars) towards a monolayer consisting of two cell types resembling type I and type II pneumocytes.Conclusions The porcine alveolar epithelial primary cell culture holds promise for drug transport studies, because it shares major hallmarks of the mammalian alveolar epithelium and it is easily available and scaled up for drug screening.     

β-胡萝卜素与香烟烟气颗粒物对体外大鼠肺细胞毒性的交互作用

[目的 ]研究 β 胡萝卜素对香烟烟气颗粒物致肺细胞毒性的交互作用。[方法 ]建立大鼠肺Ⅱ型细胞体外培养模型 ,加入 β 胡萝卜素或 /和香烟烟气颗粒物用MTT比色法检测细胞活性。[结果 ] β 胡萝卜素剂量在 0 1～ 0 5 μg/ml时 ,肺细胞活性明显增加 ;剂量在 1 0～ 2 0 μg/ml时 ,肺细胞活性明显降低。β 胡萝卜素在 0 2 μg/ml剂量时 ,可抑制香烟烟气颗粒物毒性 ;而在 0 5～ 2 0 μg/ml剂量范围内可增强香烟烟气颗粒物的细胞毒性作用。[结论 ] β 胡萝卜素在 0 1～2 0 μg/ml剂量范围内对大鼠肺细胞的生长具有先促进后抑制的双重作用。β 胡萝卜素对香烟烟气颗粒物肺细胞毒性存在交互作用 ,低浓度时表现为拮抗作用 ,高浓度时为协同作用。其交互作用可能是在细胞内实现的     

A monovalent ion-selective cation current activated by noradrenaline in smooth muscle cells of rabbit ear artery

We have studied chloride influx and efflux in a highly purified preparation of type n cells freshly isolated from adult guinea-pig lung using ³⁶Cl^–. Chloride uptake was time-dependent, saturable (K_m<10 mM) and was inhibited by 4,4-diisothiocyanatostilbene-2,2-disulphonic acid (DIDS; K_i80 M). In the absence of external chloride (substituted by gluconate), ³⁶Cl^– uptake exhibited an overshoot above equilibrium. The rate of ³⁶Cl^– entry was strongly inhibited by addition of external nitrate; sulphate was a weaker inhibitor. ³⁶Cl^– efflux was stimulated by external bromide > bicarbonate chloride citrate; and was inhibited by proprionate > acetate > oxalate. Although the chloride channel blocker 4-nitro-2-(3-phenylpropylamino)benzoate (0.14 mM) caused an inhibition, ³⁶Cl^– influx did not appear to be electrogenic. These data are compatible with the existence of a substantial electroneutral anionexchange pathway for chloride transport in freshly isolated adult type II pneumocytes.     

Effect of air pollutants on the pulmonary surfactant system

Air pollutants have been recognized to influence the structure and function of the surfactant system. Agents that have received the most attention include ozone, nitrogen dioxide, hyperoxia, diesel exhaust, tobacco smoke, silica and fibrous materials such as asbestos. The deleterious effects of air pollutants on the surfactant system depend on the size of the agent, on its solubility in aqueous solutions and chemical reactivity and on its concentration and the duration of exposure. Hereby the following general rules apply: the smaller the agent's size and the less water soluble the pollutant is, the greater the tendency to reach the alveoli during breathing. In addition, the reactivity also determines the depth of penetration into alveoli. Compounds with high reactivity such as O₃, which also fulfil the earlier rules, will react with the upper respiratory tract compared with compounds with slightly reduced reactivity, such as NO₂, which will penetrate the alveoli. The common consequence of exposure to air pollutants is an accumulation of surfactant phospholipids and surfactant-specific proteins in the bronchoalveolar lavage fluid. These components also are structurally altered, mainly by oxidant gases, resulting in impairment of their biological activity. Thus, for surfactant phospholipids, there is impaired adsorption to the air–liquid interface due to oxidation of their fatty acids. Also, surfactant protein A, regarded as a modulator of the surfactant system, shows impaired functions after exposure to oxidants. It is likely that in addition to the effects described in this review not all effects are known because the molecular effects of several key components (e.g SP-B and C) have not been well studied.