Studies of bronchoalveolar lavage cells and fluids in pulmonary sarcoidosis. II. Enhanced capacity of bronchoalveolar lavage fluids from patients with pulmonary sarcoidosis to induce cell movement in vitro

The ability to increase the motility of endothelial cells in vitro is a property common to most if not all angiogenesis-inducing factors. Because bronchoalveolar lavage (BAL) cells from patients with pulmonary sarcoidosis have an enhanced capacity to induce neovascularization, the BAL fluids from these patients were assessed for their effect on human and murine endothelial cells and fibroblasts obtained from a variety of tissue sources. A recently developed computer-assisted image analysis system was used to determine the extent and pattern of cell migration in a microwell screening assay. Data were obtained for BAL fluids from 10 patients with pulmonary sarcoidosis and from five normal volunteers. BAL supernatants from patients with active sarcoidosis showed an enhanced (2- to 8-fold) capacity to induce chemokinesis of both endothelial cells and fibroblasts, as measured by increased area of migration and polarized cell movement. There was a marked heterogeneity in the motility of cells from different organ origins, but enhanced cell movement was observed with both endothelial cells and fibroblasts. In contrast, BAL fluids from normal and sarcoid patients were similar in their effect on muscle cells and urothelial cells, whereas pericytes, which responded to BAL fluids from normal subjects or patients with nongranulomatous pulmonary disease, were inhibited by BAL fluids from patients with pulmonary sarcoidosis. The induction of endothelial cell movement in vitro induced by individual supernatants generally correlated with the capacity of BAL cells from these patients to induce angiogenesis in vivo. We suggest that the cell migration-inducing factors found in BAL fluids obtained from patients with pulmonary sarcoidosis may play a significant role not only in recruiting cells for granuloma formation in the lung but more generally in the microangiopathies of systemic sarcoidosis.