Dust/Lung Interaction

"The dust/lung research of the Center has several long-range objectives:* better methods for the early diagnosis of coal workers' pneumoconiosis (CWP);* methods to modify the disease process;* tests to identify toxic products; and* tests to identify individuals with heightened susceptibility to pneumoconiosis.A major immediate objective is to define the mechanism of dust-induced lung disease. This means determining:* dust characteristics that are important in causing lung diseases;* important interactions between dust and lungs; and* earliest detectable stages of the disease.Several of the Center's projects involve exposing lung cells in culture (in vitro) or animal lungs (in vivo) to samples of the suite of characterized mineral dusts described earlier. The responses of the lung cells or tissues to the dusts are being studied in order to better understand how inhaled dusts cause lung disease.One project is studying the effect of dust exposure on the production of mucus by rat tracheal explants in vitro. Mucus is a major factor in clearing inorganic dusts from the lung. Results thus far have shown that exposure of tracheal cultures to coal dust caused a decrease in micin production in comparison to parallel cultures without dust. To examine the effect of in vivo coal dust exposure, rats were maintained in an inhalation chamber for two weeks, and control rats were in an identical, but dust-free chamber. Tracheal explants results indicate that the effect of in vivo dust exposure is similar to that noted in the in vitro experiments.Pulmonary alveolar macrophages (PAMs) are a key component of the lung's response to inhaled particulates, and they play several important roles in pulmonary inflammatory and repair processes. PAMs are the cells that actually ingest dust particles. Other studies have shown that they play a critical role in the development of silicosis and asbestosis. The Center is studying the effect of dust exposure on the release of oxygen free radicals (superoxide) by PAMs. Intercellular production of superoxide occurs when PAMs phagocytize particles, such as inhaled bacteria, and is an essential mechanism by which PAMs kill ingested, bacteria. A number of complex physiological events occur during this process which are not clearly understood. It is thought that PAMs containing indigestible materials, such as mineral dusts, overproduce superoxide, or inappropriately release it into the surrounding tissues. If true, this would cause toxicity to surrounding lung cells by peroxidation of the lipids in the cell membranes. In vitro exposure of PAMs to low or high doses of kaolin is inert. Preliminary studies indicate that coating the quartz particles with a surfactant reduces toxicity."