Mechanisms of action of poorly soluble particulates in overload-related lung pathology.

For reasons that are unclear, poorly soluble particulates are associated with the development of inflammation, fibrogenesis, and carcinogenesis in the rat. The pathogenesis of these changes may be triggered by distinct or species-specific cellular responses to inhaled particulates in a manner similar to known fibrogenic and carcinogenic fibers, such as asbestos. Data reviewed here suggest that generation of oxidants by poorly soluble particulates is a key factor in the initiation of inflammation and generation of chemokines and cytokines in the rat. These substances then cause hyperplasia of epithelial cells and fibroblasts. The diminished or lack of proliferative responses by poorly soluble particulates in mice and primates, in comparison to rats, may be reflected by intrinsic differences in their oxidant-generating capacities or repair after oxidant injury or DNA damage.