Fibronectin and procollagen 3 levels in bronchoalveolar lavage of asbestos-exposed human subjects and sheep

Abstract

To evaluate the potential interest of levels of fibronectin and procollagen 3 in bronchoalveolar lavage fluid as markers of fibrogenic activity, we characterized the time course of changes in fibronectin and procollagen 3 levels in the tracheal lobe of sheep exposed to nonfibrogenic and fibrogenic materials. We correlated these observations with those of bronchoalveolar lavage in long-term asbestos workers in various stages of disease activity. Following studies before exposure, the tracheal lobe of three groups of 24 sheep were exposed once to 100 ml of phosphate-buffered saline solution (PBS), to 100 mg of latex beads in 100 ml of PBS, or to 100 mg of chrysotile fibers in 100 ml of PBS. Bronchoalveolar lavages were obtained at 0, 1, 2, 4, 8, and 12 months after exposure, and four or five sheep per group were killed after each lavage for histopathologic analysis. Fibronectin in bronchoalveolar lavage fluid increased significantly only in the asbestos-exposed sheep to values two to three times above controls or latex-exposed sheep and remained elevated during the 12 months of the study. Levels of procollagen 3 in bronchoalveolar lavage fluid were increased significantly only during the first two months following exposure in the asbestos-exposed sheep only. In the asbestos workers without disease, levels of fibronectin and procollagen 3 in bronchoalveolar lavage fluid were comparable to controls, but these levels were significantly elevated in those with asbestos-associated alveolitis or asbestosis. This study documents that the measurement of levels of fibronectin and procollagen 3 in bronchoalveolar lavage fluid assesses fibrogenic activity of alveolitis and should be useful to predict its progression in a fibrotic process. In asbestos workers the potential use of these markers is primarily related to early detection of asbestos-induced pulmonary injury.