Pulmonary surfactant interaction with respirable dust.
Wallace-WE Jr.; Keane-MJ; Vallyathan; Ont-T-M; Castranova-V
Proceedings of the Coal Mine Dust Conference, Morgantown, West Virginia, October 8-10, 1984. Peng, SS, ed., Morgantown, WV: West Virginia University, 1984 Oct; :180-187
Inhalation of certain forms of silica, asbestos and some other respirable dusts can result in pulmonary fibrosis, characterized by destruction of the surfaces of alveoli and respiratory bronchioles. Fibrous thickening of the alveolar septa decreases the lung's capacity for gas exchange. Pulmonary macrophage damage by respired dust may initiate the fibrotic response. In one proposed mechanism, dust particles interact with the plasma membrane of a macrophage. This damages the cell or induces some hyperactivity of the cell, resulting in excessive release of lysosomal enzymes and reactive forms of oxygen. These reactive enzymes or radicals then damage the alveolar surface epithelial cells. A second mechanism has also been proposed in which dust damage to the macrophage causes the release of mediator substances which induce pulmonary fibroblast cell proliferation and increased collagen synthesis. This produces fibrous tissue in the terminal air spaces. Mineral surface interactions with plasma membrane lipoproteins have been proposed as a mechanism of lytic damage of pulmonary cells by silica dust in numerous models. The significance of dust surface properties has been further revealed in studies showing significant changes in dust induced cytotoxicity as a function of dust surface crystallinity and organic or inorganic contamination or coating of mineral surfaces. Such modification of the mineral surface might interfere with surface sites responsible for the toxicity of dusts for pulmonary macrophages, thus interrupting the early stages of the process of fibrosis. In vitro cellular assay systems using-erythrocyte hemolysis or the release of macrophage cytosolic or lysosomal enzymes following dust challenge, have been used to analyze the initial mechanism of dust damage to cells. However, the ability of these assays to predict the pulmonary disease producing potential of various dusts is imperfect owing to some "false positive" results. These assays as performed are therefore questionable models for the initial lesion in pneumoconiosis or silicosis. In particular, kaolin frequently is found to have comparable biological activity to silica quartz in these assays. Silica and kaolin have distinctly different fibrogenic potentials. Silica is highly fibrogenic, resulting in both acute and chronic silicosis. Some epidemiological data and animal experimentation data have indicated that long term exposure to kaolin can result in pneumoconiosis; however, kaolin is relatively benign as compared to silica. Kaolin is also of interest because it is one of the major mineral inclusions in Eastern U.S. bituminous coals. We have observed that exposing respirable sized native silica or kaolin for two hours to pulmonary macrophages results in a greater enzyme release for kaolin exposures, on a dust mass basis. Exposure of erythrocytes to the dusts also results in greater levels of hemolysis by kaolin for equal mass respirable dust doses. Therefore, these results do not correlate positively with known disease inducing potentials of the two dusts. Characterization of physical and chemical surface properties of dusts involved in occupational exposures, and characterization of the alteration of those surface properties which are likely to occur upon deposition of the dust in the lung, should improve the identification of respiratory disease hazards. Inhaled dust particles deposited in the lower respiratory tract will come in contact with pulmonary surfactant. This surfactant forms a surface film on and emulsion in the liquid hypophase coating of the alveoli and respiratory bronchioles. The primary constituent of this pulmonary surfactant is the lipid diacyl glycerophosphorylcholine, lecithin. Because this lipid is also a major component of ce11 membranes, it is possible that surfactant can interact with mineral dust to alter its interaction with macrophages and other pulmonary cells and, thus, its pathogenicity. Adsorption of dipalmitoyl lecithin from emulsion in physiological saline by kaolin, a layered alumino-silicate, does occur. In addition, silica also exhibits the capacity to absorb surfactant-like material. Our earlier research quantified the adsorption of dipalmitoyl lecithin emulsion in physiological saline at 370C by a kaolin respirable sized dust of 26 m2/g specific surface area. In the concentrated emulsion range, up to 18 weight % lecithin to kaolin was adsorbed. It has been suggested that such adsorption of lipids may alter the cytotoxicity of dusts. We have been studying this question, using dipalmitoyl lecithin in physiological saline to pretreat dusts to model the initial contact of respired dust with pulmonary surfactant. First, we monitored cytotoxicity using two assay systems. The release of three enzymes from pulmonary macrophages were used as indicators of cell death or damage following dust exposure in vitro. Lactate dehydrogenase-TLDH) and two lysosomal enzymes, beta-glucuronidase (beta-GLUC) and beta-N-acetyl glucosaminidase (beta-NAG) , were measured in the external cell medium following dust exposure and compared with total intracellular levels for unexposed controls. Second, hemolysis of erythrocytes was used as a specific indicator for external cell membrane lysis by dusts. These assays were used with native silica and kaolin dusts in contrast to experiments using lecithin treated silica and kaolin. We present here some representative data obtained in studies of silica and kaolin respirable sized dusts. Complete data will be reported elsewhere.
Silica-dusts; Quartz-dust; Exposure-assessment; Dust-particles; Dust-exposure; Airborne-particles; Airborne-dusts; Particulate-dust; Pulmonary-system-disorders; Respiratory-system-disorders; Respiratory-irritants; Lung-disease; Lung-irritants; Fibrous-dusts; Surfactants; Silicosis; Silicon-compounds; Silicates
Proceedings of the Coal Mine Dust Conference, Morgantown, West Virginia, October 8-10, 1984