Effects of cigarette smoke exposure on retention of asbestos fibers in various morphologic compartments of the guinea pig lung

Abstract

For investigation of mechanisms whereby smoking might potentiate asbestos-related disease, guinea pigs were given 0.5 mg UICC amosite by intratracheal instillation. Half the animals were subsequently exposed to cigarette smoke. Animals were sacrificed at 1 day, 7 days, and 1 month after exposure. Lungs were lavaged and macrophages separated from the lavage fluid. Lung fiber concentration, numbers of fibers in macrophages, and fiber sizes from tissue (TFs), macrophages (MFs), and macrophage-free lavagate (FFs) were determined by electron microscopy. Smoke-exposed animals retained greater numbers of fibers in lung tissue by 1 month but had greater total numbers of fibers in macrophages at all time periods. In both smokers and nonsmokers, fibers in the three morphologic compartments had distinctly different lengths: the longest fibers were found associated with the lung tissue; the macrophages always contained the shortest fibers; and the macrophage-free lavagate had fibers of intermediate size. However, fiber widths and aspect ratios did not show the same clear separation by anatomic compartment, suggesting that in both smoking and nonsmoking animals length is the size parameter which is most important in determining fiber clearance. Smoking did not affect the lengths of MFs but did produce a progressive reduction in the lengths of FFs and TFs with time. These data indicate that smoking causes a marked increase in the number of fibers retained in the lung within macrophages and suggest that either macrophage removal via the mucociliary escalator or macrophage mobility is impaired by cigarette smoke. However, smoking does not change the sizes of fibers in macrophages and does not appear to depress phagocytic capacity. These observations imply that failure of macrophage clearance and subsequent re-release of fibers into the medium may at least partially explain the changes in fiber sizes and eventual increases in tissue fiber concentrations in smoke-exposed animals.