The understanding of the molecular mechanism by which quartz exerts its fibrogenic activity is the goal of this project. Quartz fibrogenesis is a two stage mechanism mediated by the alveolar macrophage. Factor(s) released by macrophages after phagocytosis of quartz causes fibroblasts to increase collagen synthesis. The ability of the quartz surface to alter the permeability of the phago-lysosomal membrane is thought to lead to the release of the collagen stimulating factor(s). The focus of this project is on the interaction of the quartz surface with cell membranes. Specifically: (1). The importance of surface charge and hydrogen bonding ability of the quartz surface in membrane interaction; (2). Identification of compounds which inhibit this interaction; (3). Identification of quartz and membrane receptors by use of inhibitors; (4). Extension of these studies to the silica polymorphs-tridymite and cristobalite. The pneumoconiosis and mineral-related malignancies (e.g. with asbestos) rank as one of the most important factors in occupational lung diseases. Quartz hemolysis and macrophage cytotoxicity will be used as a bioassay. Various quartz samples from different geological locations (which have been characterized for surface charge, hydrogen bonding ability, size distribution, etc.) will be used to challenge erythrocytes and macrophages. The importance of these variables in hemolysis and cytotoxicity will be determined. Inhibitors will be used to further characterize possible receptors. This study would enable a molecular understanding of the critical step in which quartz initiates the fibrogenic sequence.
| Langer, A M; Nolan, R P; Constantopoulos, S H et al. (1987) Association of Metsovo lung and pleural mesothelioma with exposure to tremolite-containing whitewash. Lancet 1:965-7 |
| Nolan, R P; Langer, A M; Weisman, I et al. (1987) Surface character and membranolytic activity of rutile and anatase: two titanium dioxide polymorphs. Br J Ind Med 44:687-98 |
