The present report extends earlier investigations on mechanisms of pulmonary injury associated with the presence of respirable particles in the bronchoalveolar milieu. In the animal model, this study documents that asbestos-associated alveolitis which progresses to peribronchiolar and endobronchiolar fibrosis (the fundamental lesion of asbestosis) is associated with significant early increase in the level of procollagen 3 in bronchoalveolar lavage fluid and a sustained increase in the fibronectin level, which do not occur in the nonfibrosing and regressive latex-associated alveolitis. In asbestos workers with clinical and lavage evidences of alveolitis, levels of procollagen 3 and fibronectin are similarly increased in bronchoalveolar lavage fluid, which should improve our understanding of disease activity in asbestos workers.
In the sheep tracheal lobe, this study documents that after a single high-dose exposure to asbestos, there are severe derangements of the bronchoalveolar milieu and activation of a chronic sustained alveolar, peribronchiolar and endobronchiolar inflammatory process which evolves to fibrosis. On bronchoalveolar lavage the increased macrophage and neutrophil cellularity is associated with increased fibronectin, a glycoprotein produced locally by the macrophage, known to be chemotactic and an attachment factor for fibroblasts and a stimulant for fibroblast replication in association with another macrophage-derived fibroblast growth factor (MDFGF). In the asbestos-associated alveolitis in sheep, we have reported enhanced production of MDFGF and macrophage-derived neutrophil chemotactic factor (MDNCF). Because these three macrophage-derived factors (fibronectin, MDFGF, and MDNCF) are currently thought to have major roles in the pathogenesis of pulmonary fibrosis, our data from sheep suggest that these factors contribute to maintain the alveolitis on a long-term basis and lead to its progression to asbestosis. The mechanisms which activate the macrophage to produce these factors are likely related to the prolonged retention of asbestos fibers in the bronchoalveolar milieu, as suggested by our previous study of alveolar clearance of chrysotile in the sheep model. In the model, we have shown that one year after cessation of exposure, 11 percent of the fibers shorter than 8μ, 32 percent of the fibers with length in the range of 8μ to 20μ, and 50 percent of the fibers longer than 20|i were still recoverable by pulmonary lavage. The persistence of these fibers in the bronchoalveolar milieu may constitute the determinant factor for maintenance of activated macrophages and alveolitis due to the concern of My Canadian Pharmacy.